Oncology Research 27(5) Abstracts

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Oncology Research, Vol. 27, pp. 515-524, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15166183598572
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Upregulation of miR-324-5p Inhibits Proliferation and Invasion of Colorectal Cancer Cells by Targeting ELAVL1

Chijiang Gu,* Mingyuan Zhang,* Weiliang Sun,* and Changzheng Dong†

*Department of Gastrointestinal Surgery, Affiliated Yinzhou Hospital of Ningbo University, Ningbo City, Zhejiang Province, P.R. China
†School of Medicine, Ningbo University, Ningbo City, Zhejiang Province, P.R. China

Colorectal cancer (CRC) is a common clinical cancer that remains incurable in most cases. miRNAs are reported to play a part in the development of various tumors. In the present study, we found that miR-324-5p was downregulated in CRC cells, while ELAV (embryonic lethal, abnormal vision, Drosophila)-like protein 1 (ELAVL1) showed a higher expression. miR-324-5p transfection significantly inhibited the proliferation as well as invasion in both SW620 and SW480 cells. miR-324-5p mimic transfection markedly decreased the expression of ELAVL1. Luciferase reporter gene assay confirmed that ELAVL1 is a direct target of miR-324-5p. Furthermore, cancer invasion factors uPAuPAR, and MMP-9 were found to drop significantly in miR-324-5p-transfected groups. To conclude, our findings indicate that miR-324-5p may play a suppressive role in colorectal cell viability and invasion, at least in part, through directly targeting ELAVL1. Therefore, miR-234-5p might function as a promising candidate for CRC treatment and deserves deeper research.

Key words: Colorectal cancer (CRC); miR-324-5p; Proliferation; Invasion; (Embryonic lethal, abnormal vision, Drosophila)-like protein 1 (ELAVL1)

Address correspondence to Weiliang Sun, Department of Gastrointestinal Surgery, Affiliated Yinzhou Hospital of Ningbo University, Baizhang East Road No. 251, Jiangdong District, Ningbo City, Zhejiang Province, 315000, P.R. China. Tel: +86-0574-87016921. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 525-532, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15179668157803
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis

Ting Yu,*1 Lei Li,†1 Wenyan Liu,* Bailiu Ya,* Hongju Cheng,* and Qing Xin*

*Department of Physiology, Jining Medical University, Jining, Shandong, P.R. China
†Department of Diagnosis, Jining Medical University, Jining, Shandong, P.R. China

Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1α, LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia condition through suppressing cell proliferation and proliferation-related proteins (Ki-67 and PCNA) compared with the hypoxia 24 h + siRNA NC group. Further, Western blot experiments exhibited that NOX4 siRNA could downregulate the rate of p-Akt/Akt. Treatment with PI3K/Akt signaling activator IGF-1 blocked, while treatment with Akt inhibitor perifosine enhanced the inhibitory effect of si-NOX4 on glycolysis and cell growth. In summary, knockdown of NOX4 had the ability of reversing hypoxia resistance, and the major mechanism is considered to be the inhibition of glycolysis and cell growth via the PI3K/Akt signaling pathway. Therefore, NOX4 could be a novel target against hypoxia resistance in neuroblastoma.

Key words: NADPH oxidase 4 (NOX4); Hypoxia resistance; Neuroblastoma; Glycolysis; PI3K/Akt

1These authors provided equal contribution to this work.
Address correspondence to Lei Li, Department of Diagnosis, Jining Medical University, Hehua Road 16, Jining 272067, Shandong, P.R. China. Tel: 0537-2966666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 533-540, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15199489058224
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells

Xiaoying Han,*1 Jing Yang,†1 Dong Li,‡ and Zewei Guo§

*Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, P.R. China
†Department of Oncology, Xuzhou City Hospital of Traditional Chinese Medicine, Xuzhou, P.R. China
‡Department of Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
§Department of Internal Medicine, Huangshan Traditional Chinese Medicine, Huangshan, Anhui, P.R. China

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Although the mechanisms of HCC progression are not well understood, recent studies demonstrated the potential contribution of uric acid transporter SLC2A9 to tumor suppression. However, the roles and underlying mechanisms are still unknown. We aimed to study the roles and mechanisms of SLC2A9 in HCC. The present study showed that SLC2A9 expression was decreased in human HCC tissues and cell lines. In addition, overexpression of SLC2A9 inhibited HCC cell proliferation. SCL2A9 induced HCC cell apoptosis by inhibiting the expression of caspase 3. Our study also revealed that upregulation of SLC2A9 reduced intracellular reactive oxygen species (ROS) accumulation. Furthermore, SLC2A9 increased the mRNA and protein expression of tumor suppressor p53 in HCC cells. Probenecid inhibits SLC2A9-mediated uric acid transport, which promotes cell proliferation, inhibits cell apoptosis, induces intracellular ROS, and decreases the expression of p53 in HCC cells. Therefore, the present study demonstrated that SLC2A9 may be a novel tumor suppressor gene and a potential therapeutic target in HCC.

Key words: SLC2A9; HCC; Cell proliferation; Apoptosis; ROS, p53

1These authors provided equal contribution to this work.
Address correspondence to Dong Li, Department of Oncology, Xuzhou Central Hospital, No. 199 South Jiefang Road, Quanshan District, Xuzhou, Jiangsu 221009, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 541-549, 2019
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DOI: https://doi.org/10.3727/096504018X
15234931503876
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Long Noncoding RNA LINC01296 Harbors miR-21a to Regulate Colon Carcinoma Proliferation and Invasion

Kecheng Wang,* Meng Zhang,† Cong Wang,† and Xiaofei Ning*

*Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical College, Jining, Shandong, P.R. China
†Department of Medical Ultrasonography, Affiliated Hospital of Jining Medical College, Jining, Shandong, P.R. China

Increasing evidence has demonstrated that aberrant expressions of long noncoding RNAs (lncRNAs) are closely correlated to various malignancies, as well as colon carcinoma (CC). The aim of this study was to investigate the role of lncRNA long intergenic noncoding RNA 001296 (LINC01296) in tumorigenesis of CC. The result of the quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that LINC01296 was upregulated in CC cancerous tissues and cell lines compared to adjacent normal tissue and normal liver cell lines. LINC01296 overexpression was associated with poor prognosis and lower survival rate. Moreover, LINC01296 silencing inhibited the proliferation and invasion of CC cells in vitro detected by epithelial–mesenchymal transition (EMT). Bioinformatics analysis revealed that miR-21a targeted the 3ʹ-UTR of LINC01296. Rescue experiments confirmed that miR21a could reverse the function of LINC01296 on CC cells. Together, our findings indicated that overexpression of LINC01296 is associated with poor survival of CC patients and promotes CC cell progression by regulating miR-21a, providing a prognostic biomarker and therapeutic target.

Key words: miR-21a; Colon carcinoma (CC); Long noncoding RNAs (lncRNAs); LINC01296; Proliferation; Invasion

Address correspondence to Xiaofei Ning, Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical College, No. 79 Guhuai Road, Jining, Shandong 272000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 551-556, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15291727589740
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Regorafenib
-Induced Hand–Foot Skin Reaction Is More Severe on the Feet Than on the Hands

Yuma Nonomiya,* Takashi Yokokawa,† Kazuyoshi Kawakami,† Kazuo Kobayashi,† Takeshi Aoyama,† Tomomi Takiguchi,† Takahito Sugisaki,† Kenichi Suzuki,† Mitsukuni Suenaga,‡ Takeru Wakatsuki,‡ Kensei Yamaguchi,‡ Yoshikazu Sugimoto,* and Toshihiro Hama†

*Division of Chemotherapy, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan
†Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
‡Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan

Regorafenib is a multikinase inhibitor for the treatment of metastatic colorectal cancer. Regorafenib-induced hand–foot skin reaction (HFSR) is a common side effect during treatment. The reported frequency of HFSR was 80% (grade 3: 28%) in the Japanese subpopulation in the CORRECT trial; however, more detailed data regarding HFSR in terms of onset and sites of susceptibility are unclear. Additionally, the risk factors for regorafenib-induced severe HFSR are unknown. The aim of this study was to compare HFSR between the hands and feet and identify preexisting risk factors for severe HFSR in Japanese patients receiving regorafenib. We retrospectively examined the onset and severity of HFSR on the hands and feet of patients with metastatic colorectal cancer treated with regorafenib from May 2013 to October 2015 in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In addition, we examined the possible association between preexisting clinical factors and severe HFSR. Our results showed that no significant difference in the incidence of HFSR of any grade was observed between the hands (71%) and feet (74%) (p = 0.63). The incidence of grade 3 HFSR was more frequent on the feet (33%) than on the hands (8%) (p< 0.01). The onset of grade 3 HFSR was earlier on the feet than on the hands (p < 0.001). No preexisting risk factor was identified. Our findings indicate that severe HFSR was more prevalent on the feet than on the hands, suggesting the need for appropriate screening for early detection and treatment of regorafenib-induced HSFR.

Key words: Regorafenib; Hand–foot skin reaction (HFSR); Pharmaceutical outpatient clinic; Risk factors

Address correspondence to Toshihiro Hama, Ph.D., Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Tel: +81-3-3570-0214; Fax: +81-3-3570-0216; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 557-564, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15264647024196
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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NLRP3 Promotes Glioma Cell Proliferation and Invasion via the Interleukin-1β/NF-κB p65 Signals

Liping Xue,*1 Bin Lu,†1 Bibo Gao,‡ Yangyang Shi,‡ Jingqi Xu,‡ Rui Yang,‡ Bo Xu,‡ and Peng Ding‡

*Department of Ophthalmology, Yunnan No. 2 Provincial People’s Hospital, Kunming, Yunnan, P.R. China
†Department of Neurosurgery, Huzhou Central Hospital, Huzhou, Zhejiang, P.R. China
‡Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China

Because of the characteristics of high invasiveness, relapse, and poor prognosis, the management of malignant gliomas has always been a great challenge. Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) is a crucial component of the NLRP3 inflammasome, a multiprotein complex that can trigger caspase 1/interleukin-1 (IL-1)-mediated inflammatory response once activated and participates in the pathogeny of diverse inflammatory diseases as well as cancers. We examined the function of NLRP3 in the development of glioma. Glioma cells were treated with NLRP3 interference or overexpression vectors, recombinant IL-1β, IL-1β antibody, and NF-κB inhibitor. Cell proliferation and invasion were assessed by CCK-8 and Transwell assays. Gene expression was detected by PCR, Western blot, and ELISA. NLRP3 and NF-kB p65 increased and were positively correlated in glioma tissues. NLRP3 knockdown suppressed glioma cell growth and invasion with the decrease of IL-1β and NF-κB p65. Conversely, forced expression of NLRP3 promoted cell growth. NLRP3 silencing suppressed ectogenous IL-1β-elevated cell proliferation and invasion, whereas IL-1β elimination impaired the proproliferation effect of NLRP3 hyperexpression. Furthermore, NF-κB blockage abrogated IL-1β and NLRP3 hyperexpression increased cell growth and invasion. NLRP3 promoted the growth and invasion of gliomas via the IL-1β/NF-κB p65 signals.

Key words: Glioma; NLRP3; Interleukin-1β (IL-1β); NF-κB

1These authors provided equal contribution to this work.
Address correspondence to Peng Ding, Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan 650032, P.R. China. Tel: +86-0871-65324888-2452; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 565-573, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15313896322888
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Efficacy and Safety of CalliSpheres
® Drug-Eluting Beads Transarterial Chemoembolization in Barcelona Clinic Liver Cancer Stage C Patients

Yaohong Liu, Wensou Huang, Mingji He, Hui LianYongjian GuoJingjun Huang, Jingwen Zhou, and Kangshun Zhu

Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China

This study aimed to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Barcelona Clinic Liver Cancer (BCLC) stage C liver cancer patients. In 39 patients with BCLC stage C liver cancer, after the first cycle of DEB-TACE, 2 (5.1%) and 24 (61.5%) patients achieved complete response (CR) and partial response (PR) to give an overall objective response rate (ORR) of 66.7%. With respect to the second cycle of therapy, the ORR was higher in patients receiving DEB-TACE compared with those receiving cTACE (57.1% vs. 11.1%). After the first cycle of DEB-TACE treatment, the percentages of abnormal albumin (ALB), total protein (TP), total bilirubin (TBIL), and alanine aminotransferase (ALT) worsened at 1 week and recovered at 1 month. The number of patients with abnormal aspartate aminotransferase (AST) did not increase at 1 week but elevated at 1 month. After the second cycle of DEB-TACE or cTACE treatment, no difference was observed between cTACE and DEB-TACE in terms of all adverse events (AEs) at all visits, and most of the AEs did not change after the second cycle in both groups. The most common AEs after the first and second treatment cycles were pain, fever, and nausea/vomiting. These results demonstrate that DEB-TACE offers patients with BCLC stage C liver cancer a clinically active short-term treatment that is safe and relatively well tolerated.

Key words: Clinical efficacy; Safety; Drug-eluting beads transarterial chemoembolization (DEB-TACE); Barcelona Clinic Liver Cancer (BCLC) stage C; Liver cancer

Address correspondence to Kangshun Zhu, Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, Guangdong, P.R. China. Tel: +86-020-34152781; Fax: +86-020-34153709; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 575-582, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15344979253618
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

Kai Zhang,* Huajun Chen,† Ye Wang,‡ Lin Yang,§ Chengzhi Zhou,¶ Weiqiang Yin,# Guangsuo Wang,§ Xinru Mao,** Jianxing Xiang,** Bing Li,** Tengfei Zhang,** and Shihong Fei*

*Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
†Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P.R. China
‡Department of Respiratory Medicine, West China Hospital, Chengdu, Sichuan, P.R. China
§Department of Thoracic Surgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, P.R. China
¶State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China
#Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China
**Burning Rock Biotech, Guangzhou, Guangdong, P.R. China

RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequent fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET
+ patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration, and concomitant EGFR oncogenic alterations were identified in seven patients. Moreover, an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged lung cancers in China. It might be helpful to guide clinicians for more effective personalized diagnostic and therapeutic approaches.

Key words: RET rearrangement; Lung cancer; Adenocarcinoma; Clinical characteristics; Concurrent gene alteration

Address correspondence to Shihong Fei, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, P.R. China. Tel: +86 027-85726114; Fax: +86 027-85726114; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 583-592, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15368325811545
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Comparison of Treatment Response and Survival Profiles Between Drug-Eluting Bead Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients: A Prospective Cohort Study

Ping Wen,* Sheng-Duo Chen,* Jia-Rui Wang,† and Ying-He Zeng*

*Division of Liver Disease, Hubei Provincial Hospital of TCM, Garden Hill School District, Wuhan, Hubei, P.R. China
Huazhong University of Science and Technology Press, Wuhan, Hubei, P.R. China

This study evaluated the difference in treatment response and survival profiles between drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) treatments in Chinese hepatocellular carcinoma (HCC) patients. A total of 120 HCC patients were consecutively enrolled in this prospective cohort study, which showed that DEB-TACE achieved higher complete response (CR) (30.8%) compared with cTACE (7.4%) with no difference in overall response rate (ORR) for patients treated with DEB-TACE and cTACE (80.8% vs. 73.5%). In addition, DEB-TACE was associated with a lower rate of progressive disease (PD) compared with cTACE (1.9% vs. 11.8%). With respect to survival, patients in the DEB-TACE group achieved median progression-free survival (PFS) of 15 months (95% CI 12–18 months), which was longer than the cTACE group [median PFS 11 months (95% CI 10–12 months)]. Median overall survival (OS) was also longer with DEB-TACE [25 months (95% CI 22-28 months)] when compared with cTACE [21 months (95% CI 18–24 months)]. Univariate and multivariate logistic regression analysis showed that DEB-TACE was an independent predictive factor for achieving CR. Univariate Cox’s regression analysis revealed that DEB-TACE was a predictive factor for prolonged PFS and OS, while multivariate analysis demonstrated that DEB-TACE was not an independent factor for predicting PFS or OS. In conclusion, we found that DEB-TACE achieved higher treatment response and prolonged survival compared with cTACE in Chinese HCC patients.

Key words: Hepatocellular carcinoma (HCC); Overall survival; Response rate; Univariate analysis; Drug-eluting bead-transarterial chemoembolization (DEB-TACE); Treatment response; Conventional transarterial chemoembolization (cTACE); Progression-free survival; Multivariate analysis

Address correspondence to Shengduo Chen, Division of Liver Disease, Hubei Provincial Hospital of TCM, Garden Hill School District, 4 Garden Hill, Wuhan 430061, P.R. China. Tel: +86-27-88929215; Fax: +86-27-88929210; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Jiarui Wang, Huazhong University of Science and Technology Press, Wuhan, Hubei, P.R. China. Tel: +86-27-88929215; Fax: +86-27-88929210; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 593-600, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15051723858706
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Ursolic
Acid Attenuates TGF-β1-Induced Epithelial–Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling

Jun Shan Ruan,*† Huan Zhou,* Lin Yang,‡ Ling Wang,* Zong Sheng Jiang,§ Hong Sun,* and Shao Ming Wang*†

*Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian, P.R. China
†Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, Fujian, P.R. China
‡Fujian Medical University Cancer Hospital, Fujian, P.R. China
§The School of Pharmacy, Fujian Medical University, Fujian, P.R. China

Transforming growth factor-β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1–integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolicacid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway-mediated integrin aVb5 expression, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.

Keywords: Non-small cell lung cancer (NSCLC); Epithelial–mesenchymal transition (EMT); Ursolic acid; Metastasis

Address correspondence to Dr. Jun Shan Ruan, Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, No. 134 East Road, Gulou District, Fuzhou, Fujian Province 350001, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dr. Shao Ming Wang, Medical University, Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, No. 134 East Road, Gulou District, Fuzhou, Fujian Province 350001, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 601-611, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15399945637736
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Baicalein
Exerts Anticancer Effect in Nasopharyngeal Carcinoma In Vitro and In Vivo

Jiandong GuoHuihua You, and Dong Li

Department of Otorhinolaryngology—Head and Neck Surgery, Jinhua Central Hospital, Jinhua, P.R. China

Baicalein, an active ingredient separated from Astragalus membranaceus, has shown its anticancer ability in various cancers. However, its effect on nasopharyngeal carcinoma has not been explored yet. The present study aimed to investigate the effect of baicalein on the growth, proliferation, apoptosis, and cell cycle of human nasopharyngeal carcinoma cells, as well as transplanted nude mouse xenograft. The results showed that baicalein inhibited the growth and proliferation of CNE1 and CNE2 cells in a time- and concentration-dependent manner. It also caused a significant increase in the number of cells in the G0/G1
phase and a decrease in the G2/M phase, thereby reducing the number of cells entering mitosis and inhibiting the proliferation of tumor cells. Baicalein also significantly induced apoptosis of CNE1 and CNE2 cells. Western blots showed that baicalein decreased the expression of Bcl-xl and Mcl-1 and increased the expression of Bax, Bad, and caspase 3, 8, and 9. In CNE1- and CNE2-transplanted tumors of mice, baicalein significantly inhibited tumor growth. In conclusion, baicalein could inhibit the growth and proliferation of human nasopharyngeal carcinoma cells, change their cell cycle, and induce apoptosis. Baicalein also effectively limits both CNE1- and CNE2-transplanted tumors in nude mice. Downregulation of Bcl-xl and Mcl-1 proteins and upregulation of Bax and Bad may be involved in the mechanism.

Key words: Baicalein; Nasopharyngeal carcinoma (NPC); Apoptosis; Cell cycle; Xenograft

Address correspondence to Jiandong Guo, Department of Otorhinolaryngology—Head and Neck Surgery, Jinhua Central Hospital, No. 351 Ming Yue Road, Jinhua, P.R. China. Tel: +(86) 15867929578; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 613-621, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15410353669149
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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PHF8 Plays an Oncogene Function in Hepatocellular Carcinoma Formation

Hong Ye,* Qing Yang,† Shujie Qi,* and Hairong Li‡

*Department of Gastroenterology, Jiaozhou People’s Hospital, Jiaozhou, Shandong Province, P.R. China
†Department of Pathology, Jiaozhou People’s Hospital, Jiaozhou, Shandong Province, P.R. China
‡Department of Traditional Chinese Medicine, Jiaozhou People’s Hospital, Jiaozhou, Shandong Province, P.R. China

Hepatocellular carcinoma (HCC) has high morbidity and mortality rates, and the number of new cases and deaths from liver cancer are increasing. However, the details of the regulation in HCC remain largely unknown. Plant homeodomain finger protein 8 (PHF8) is a JmjC domain-containing protein. Recently, PHF8 was reported to participate in several types of cancer. However, the biological function and clinical significance of PHF8 in HCC remain unknown. In this study, we investigate the role of PHF8 in HCC growth and metastasis. We used bioinformatics analysis and identified the differentially expressed PHF8 in primary HCC and metastasis HCC. Immunohistochemistry analysis demonstrated that PHF8 was expressed higher in human HCC tissues than in corresponding adjacent noncancerous tissues. Silencing PHF8 in HCC cells significantly decreased the cells’ ability of proliferation, migration, invasion, and sphere formation. On the contrary, overexpression of PHF8 promoted these properties. In addition, the analysis in vivo showed that PHF8 overexpression promoted tumor formation and metastasis in nude mice. In the end, the RNA-sequence assay showed that CUL4A is upregulated by the PHF8. Taken together, these results demonstrated that PHF8 was a novel oncogene in HCC, which may contribute to therapeutic approaches aimed at targeting components of the PHF8 and provide new insights into the mechanisms governing the developmental programs in HCC.

Key words: Hepatocellular carcinoma (HCC); PHF8; Proliferation; Metastasis

Address correspondence to Hong Ye, Department of Gastroenterology, Jiaozhou People’s Hospital, Guangzhoubei Road #88, Jiaozhou, Shandong Province 266300, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 623-628, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15420734828058
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Hsa_circ_0003998 Promotes Chemoresistance via Modulation of miR-326 in Lung Adenocarcinoma Cells

Wanjun Yu,* Weidong Peng,* Hanyun Sha,† and Jipeng Li‡

*Department of Respiratory and Critical Care Medicine, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, P.R. China
†Department of Nephrology, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, P.R. China
‡Department of Central Laboratory, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, P.R. China

Circular RNAs (circRNAs) represent a new class of noncoding RNAs that is involved in the development of cancer. However, little is known about their role in chemoresistance. In the present study, we found that hsa_circ_0003998 expression levels in lung adenocarcinoma (LAD) tissues and docetaxel-resistant cell lines (A549/DTX and H1299/DTX) were upregulated. Knockdown of hsa_circ_0003998 decreased chemoresistance, inhibited proliferation, and enhanced apoptosis in docetaxel-resistant LAD cells. Moreover, by using bioinformatics and luciferase reporter assays, we found that miR-326 was a direct target of hsa_circ_0003998. Functional analysis revealed that miR-326 mediated the effect of hsa_circ_0003998 on chemosensitivity. Our findings provide a molecular insight on understanding drug resistance in LAD cells. Therefore, inactivation of hsa_circ_0003998 or activation of miR-326 could be a novel approach for the treatment of LAD.

Key words: Circular RNA (circRNA); hsa_circ_0003998; Chemoresistance; miR-326; Lung adenocarcinoma (LAD)

Address correspondence to Jipeng Li, Department of Central Laboratory, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, 251 East Baizhang Road, Ningbo 315040, P.R. China. Fax: + 86 574 87017643; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it