Oncology Research 27(4) Abstracts

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Oncology Research, Vol. 27, pp. 399-406, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15179675206495
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Ectopic Expression of miR-147 Inhibits Stem Cell Marker and Epithelial–Mesenchymal Transition (EMT)-Related Protein Expression in Colon Cancer Cells

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

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

Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers E-cadherin and
a-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-b1 treatment significantly counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 downregulated the expression of b-catenin, c-myc, and survivin, which were related to the Wnt/β-catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/β-catenin pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells by suppressing EMT via the Wnt/β-catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment.

Key words: MicroRNA-147 (miR-147); Colon cancer; Epithelial-to-mesenchymal transition (EMT); Wnt/β-catenin pathway

Address correspondence to Kecheng Wang, Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical College, No. 89 Guhuai Road, Jining, Shandong, P.R. China. Tel: (0537)2903085; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 407-414, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15180451872087
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma

Jihong Sun,*†1 Jingjing Li,†1 Zhixian Guo,† Lu Sun,†‡ Chenghui Juan,§ Yubing Zhou,¶ Hongli Gu,† Yan Yu,† Qiuyue Hu,† Quancheng’ Kan,¶ and Zujiang Yu†

*Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
§Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
¶Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen supply, a condition known as “aerobic glycolysis,” or the “Warburg effect.” Pyruvate dehydrogenase E1
α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed that the PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry and Western blot, which was significantly associated with poor overall survival. To further analyze the function of PDHA1 in cancer cells, PDHA1 was upregulated in the HCC cell lines SMMC-7721 and HepG2. The results demonstrated that overexpression of the PDHA1 gene inhibited aerobic glycolysis with lower lactate via increased PDH activity; meanwhile, mitochondrial OXPHOS was enhanced accompanied with higher ATP and lower glucose consumption. We also found that apoptosis was promoted and intrinsic pathway proteins were increased in PDHA1-overexpressing cells. Collectively, our data indicate that reduced PDHA1 protein expression is associated with the poor clinical outcome of HCC. Upregulated PDHA1 gene expression can inhibit the Warburg effect and enhance the mitochondria-mediated apoptosis pathway.

Key words: Pyruvate dehydrogenase E1α subunit (PDHA1); Warburg effect; Apoptosis; Hepatocellular carcinoma (HCC)

1These authors provided equal contribution to this work.
Address correspondence to Quancheng’ Kan, M.D., Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Room 120, 9th Building, No. 1 Jian-She East Road, Zhengzhou 450052, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Zujiang Yu, M.D., Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, 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. 415-422, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15155538502359
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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CD47 Promotes Human Glioblastoma Invasion Through Activation of the PI3K/Akt Pathway

Xuejian Liu,*1 Xia Wu,*1 Yanming Wang,† Yuhua Li,* Xiangli Chen,* Wenchuan Yang,* and Lihua Jiang*

*Department of Oncology, Linyi Third People’s Hospital, Linyi, Shandong, P.R. China
†Department of Radiotherapy, Jinan Military Region General Hospital, Jinan, Shandong, P.R. China

Cluster of differentiation 47 (CD47) overexpression is common in various malignancies. This study investigated whether CD47 promotes human glioblastoma invasion and, if so, the underlying mechanisms involved. CD47 expression was found to be stronger in tissues of patients with glioblastoma and in various cancer cell lines than in normal controls. CD47 downregulation via siRNA suppressed invasion in vitro, whereas CD47 overexpression through plasmid transfection exerted the opposite effect. However, overexpression or knocking down of CD47 had no effect on cell proliferation. Moreover, CD47 expression was related to Akt phosphorylation at the cellular molecular level. Suppression of Akt with a specific inhibitor impaired the invasion ability of CD47-overexpressing cells, indicating that stimulation of the PI3K/Akt pathway served as the downstream regulator of CD47-triggered invasion. These results suggest that CD47 might be a useful predictor of poor prognosis and metastasis and a potential target for treating glioblastomas.

Key words: CD47; Glioblastoma; Invasion; Akt

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Xia Wu, Department of Oncology, Linyi Third People’s Hospital, Economic and Technological Development District, Huaxia Road No. 117, Linyi, Shandong 276023, P.R. China. Tel: 86-0539-8769202; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 423-429, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15030178624579
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Overexpression of LACTB, a Mitochondrial Protein That Inhibits Proliferation and Invasion in Glioma Cells

Hai-Tao Li, Dao-Yong Dong, Qiang Liu, Yi-Qin Xu, and Langbo Chen

Department of Neurosurgery, The First People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, P.R. China

LACTB, a mitochondrial protein, was ubiquitously expressed in different mammalian tissues, such as liver, heart, and skeletal muscle. It has been shown that LACTB is downexpressed in breast cancers, and it suppresses the proliferation and promotes the apoptosis of breast cancers. However, its role in the progression and prognosis of glioma remains unknown. In this study, we analyzed the clinicopathological features and outcomes of LACTB expression in 98 glioma patients and investigated the effects of LACTB overexpression on the proliferation, invasion, and angiogenesis of glioma cells in vitro. We observed a significant decrease in LACTB expression in glioma, and downexpression of LACTB is correlated with a poor prognosis of glioma patients. Moreover, Cox regression analysis reveals that the LACTB is an independent prognostic indicator for glioma patients. Overexpression of LACTB could suppress the proliferation, invasion, and angiogenesis of glioma cells. In addition, overexpression of LACTB could inhibit the expression of PCNA, MMP2, MMP9, and VEGF. Taken together, these data indicate that LACTB may serve as a promising therapeutic target for gliomas.

Key words: LACTB; Glioma; Proliferation; Invasion; Angiogenesis; Prognosis

Address correspondence to Hai-Tao Li, The First People’s Hospital of Chongqing Liang Jiang New Area, No. 199 Renxing Road, Chongqing 401121, 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. 423-429, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15201058168730
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-132 Targets FOXA1 and Exerts Tumor-Suppressing Functions in Thyroid Cancer

Xin Chen,* Mingzhe Li,† Hongwei Zhou,* and Li Zhang*

*Department of Radiology, the First Hospital of Jilin University, Changchun, Jilin, P.R. China
†China–Japan Union Hospital of Jilin University, Changchun, P.R. China

MicroRNA-132 (miR-132) has been demonstrated to be a tumor suppressor in several types of tumors. However, the expression and the role of miR-132 in human thyroid cancer are still poorly understood. The aim of the present study was to examine the potential roles and molecular mechanism of miR-132 in thyroid cancer. We found that miR-132 expression levels were significantly downregulated in thyroid cancer tissues and cell lines. Function assays showed that overexpression of miR-132 in TPC1 cells inhibited cell proliferation, migration, and invasion. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-132 in thyroid cancer cells. Knockdown of FOXA1 in TPC1 cells significantly inhibited cell proliferation, migration, and invasion, which mimicked the suppressive effect induced by miR-132 overexpression. Restoration of FOXA1 expression partially reversed the suppressive effect induced by miR-132 overexpression. Taken together, these results suggested that miR-132 acts as a tumor suppressor in thyroid cancer through targeting FOXA1.

Key word: MicroRNAs; miR-132; Thyroid cancer; FOXA1

Address correspondence to Li Zhang, Department of Radiology, the First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, Jilin, 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. 439-447, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15214994641786
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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TRIM14 Promotes Breast Cancer Cell Proliferation by Inhibiting Apoptosis

Gaowu Hu, Wei Pen, and Ming Wang

Department of General Surgery, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai, P.R. China

Tripartite motif-containing 14 (TRIM14) is abnormally expressed in several human cancers. However, the function and expression of TRIM14 in human breast cancer are still largely unknown. To understand the biological function of TRIM14 in breast cancer, we measured the expression level of TRIM14. Cell proliferation and cell apoptosis were measured after TRIM14 overexpression or knockdown. Upregulation of TRIM14 was found in human breast cancer specimens and cell lines. Reduction of TRIM14 inhibited cell proliferation but increased cell apoptosis in the BT474 and MDA-MB-231 cell lines. Further study showed that knockdown of TRIM14 upregulated the expression of BAX while downregulating the expression of BCL2. In addition, the expression of SHP-1 was increased, and the phosphorylation of STAT3 (p-STAT3) was inhibited. Conversely, overexpression of TRIM14 had the opposite effects. Additionally, cryptotanshinone, a STAT3 inhibitor, inhibited cell proliferation but increased cell apoptosis in the BT474 and MDA-MB-231 cell lines. In conclusion, TRIM14 may act as an oncogene in human breast cancer and may be a novel strategy for human breast cancer.

Key words: Apoptosis; Breast cancer; Src-homology protein tyrosine phosphatase-1 (SHP-1); STAT3; Tripartite motif-containing 14 (TRIM14)

Address correspondence to Ming Wang, Department of General Surgery, Shanghai Traditional Chinese Medicine-Integrated Hospital, No. 184 Baoding Road, Hongkou District, Shanghai 200082, P.R. China. Tel: 021-65415910, +86-18221133607; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 449-458, 2019
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DOI: https://doi.org/10.3727/096504017X
15016337254623
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3

Guoyun Li, Wei Zhang, Li Gong, and Xiaoping Huang

Department of Infectious Diseases, The First People’s Hospital of KunshanKunshan, Jiangsu Province, P.R. China

MicroRNAs, a class of endogenous noncoding RNAs, regulate gene expression at the posttranscriptional level and thus take part in multiple biological processes. An increasing number of miRNAs have been found to be dysregulated in hepatocellular carcinoma (HCC) and are involved in liver tumorigenesis. In this study, miR-125a-5p was found to be obviously downregulated much more in hepatitis B virus (HBV)-related HCC. To investigate the effects of miR-125a-5p, miR-125a-5p was overexpressed in HepG2.2.15 and HepG3X cells. The findings have indicated that overexpression of miR-125a-5p dramatically inhibited cell proliferation and induced cell apoptosis. Furthermore, overexpression of miR-125a-5p could significantly decrease the secretion of HBsAg and HBeAg. In concordance to this, the expression of ErbB3 was upregulated in human HBV-related HCC tissue, HepG2.2.15 cells, and HepG3X cells. miR-125a-5p directly targeted ErbB3 and reduced both mRNA and protein levels of ErbB3, which promoted cell proliferation and suppressed cell apoptosis in HCC cells. Our results provide new insights into the function of miR-125a-5p in HBV-related HCC. It is beneficial to gain insight into the mechanism of HBV infection and pathophysiology of HBV-related HCC.

Key words: Hepatocellular carcinoma (HCC); miR-125a-5p; Hepatitis B virus (HBV); ErbB3; Proliferation; Apoptosis

Address correspondence to Dr. Guoyun Li, Department of Infectious Diseases, The First People’s Hospital of Kunshan, No. 91 Qianjin Road, Kunshan, Jiangsu Province 215300, P.R. China. Tel: +86-0512-57501937; Fax: +86-0512-57501937; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 459-467, 2019
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DOI: https://doi.org/10.3727/096504018X
15193500663936
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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MicroRNA-664 Targets Insulin Receptor Substrate 1 to Suppress Cell Proliferation and Invasion in Breast Cancer

Liang Wu, Yuefeng Li, Jingye Li, and Deliang Ma

Department of Oncology, Linyi Central Hospital, Linyi, Shandong, P.R. China

A large number of microRNAs (miRNAs) have been previously demonstrated to be dysregulated in breast cancer (BC), and alterations in miRNA expression may affect the initiation and progression of BC. This study showed that miR-664 expression was obviously reduced in BC tissues and cell lines. Resumption of the expression of miR-664 attenuated the proliferation and invasion of BC cells. The molecular mechanisms underlying the inhibitory effects of BC cell proliferation and invasion by miR-664 were also studied. Insulin receptor substrate 1 (IRS1) was identified as a novel and direct target of miR-664. In addition, siRNA-mediated silencing of IRS1 expression mimicked the suppressive effects of miR-664 overexpression in BC cells. Rescue experiments demonstrated that recovered IRS1 expression partially antagonized the inhibition of proliferation and invasion of BC cells caused by miR-664 overexpression. Thus, miR-664 may serve as a tumor suppressor in BC by directly targeting IRS1. Moreover, miR-664 downregulation in BC may contribute to the occurrence and development of BC, suggesting that miR-664 may be a novel therapeutic target for patients with BC.

Key words: miR-664; Breast cancer (BC); Insulin receptor substrate 1 (IRS1); Proliferation; Invasion

Address correspondence to Deliang Ma, Department of Oncology, Linyi Central Hospital, No. 17 Jiankang Road, Linyi, Shandong 276400, 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. 469-474, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15267574931782
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Anemia Is a Novel Predictive Factor for the Onset of Severe Chemotherapy-Induced Peripheral Neuropathy in Lymphoma Patients Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone Therapy

Takashi Saito,*† Atsuo Okamura,‡ Junichiro Inoue,† Daisuke Makiura,† Hisayo Doi,§ Kimikazu Yakushijin,¶ Hiroshi Matsuoka,¶ Yoshitada Sakai,†# and Rei Ono*

*Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan
†Division of Rehabilitation Medicine, Kobe University Hospital, Kobe, Japan
‡Department of Medical Oncology and Hematology, Kakogawa Central City Hospital, Kakogawa, Japan
§Division of Nursing, Kobe University Hospital, Kobe, Japan
¶Division of Medical Oncology and Hematology, Kobe University, Kobe, Japan
#Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in lymphoma patients receiving R-CHOP, a drug combination therapy. Although severe CIPN may lead to reduction and/or discontinuation of the medication, predictive factors of CIPN have not been investigated sufficiently to date. We performed a retrospective exploratory research to determine associations between prevalence of severe CIPN and sociodemographic data, health characteristics, and medical conditions such as anemia at initial diagnosis. Forty patients (indolent lymphoma,
n = 9; diffuse large B-cell lymphoma; n = 31) received R-CHOP therapy from September 2009 to July 2014. The median age of patients was 58 years (range = 27–76 years). Statistical analyses were applied to the patients, who were divided into two groups: mild CIPN (no symptoms or grade 1 according to the CTCAE version 3.0 program) and severe CIPN patients (grade 2 or higher). Forward stepwise logistic regression analyses were performed using the following variables: sex, BMI, BSA, hyperglycemia, malnutrition, and anemia. Severe CIPN occurred in seven patients (17.5%). Gender and anemia remained following the stepwise procedure, and anemia predicted severe CIPN significantly (OR = 19.45, 95% confidence interval = 1.52–171.12). Our study suggests that anemia at initial diagnosis could be a predictive factor of R-CHOP-induced CIPN.

Key words: Chemotherapy-induced peripheral neuropathy (CIPN); Anemia; R-CHOP; Diffuse large B-cell lymphoma (DLBCL)

Address correspondence to Rei Ono, Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe, Hyogo 654-0142, Japan. Tel: +81-78-792-2555; Fax: +81-78-796-4509; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 475-486, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15270916676926
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Bufalin Induces Apoptosis and Improves the Sensitivity of Human Glioma Stem-Like Cells to Temozolamide

Jia Liu,* Ying Zhang,† Shulan Sun,‡ Guirong Zhang,‡ Ke Jiang,§ Peixin Sun,* Ye Zhang,* Bing Yao,* Rui Sui,* Yi Chen,* Xu Guo,* Tao Tang,* Ji Shi,* Haiyang Liang,* and Haozhe Piao*

*Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, P.R. China
†Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, P.R. China
‡Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, P.R. China
§Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, P.R. China

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.

Key words: Bufalin; Glioma; Cancer stem-like cells; Apoptosis; Telomerase; Temozolomide (TMZ)

Address correspondence to Dr. Haozhe Piao, Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute. No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, P.R. China. Tel: 86-24-3541-7846; Fax: 86-24-3541-7846; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 487-494, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15323394008784
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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GSK-3β Promotes Cell Migration and Inhibits Autophagy by Mediating the AMPK Pathway in Breast Cancer

Lu Guo,* Duankai Chen,† Xing Yin,‡ and Qingfeng Shu†

*Jinan University, Guangzhou, Guangdong, P.R. China
†General Surgery, YouJiang Medical University for Nationalities, Guangxi, P.R. China
‡Wound Regeneration and Vascular Surgery Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, P.R. China

GSK-3
β is a versatile protein kinase participating in many reactions. Currently, there is insufficient understanding of its influence on breast cancer (BC). In order to explore its influence on migration and invasion in BC, we investigated its expression in BC cell lines using qRT-PCR and Western blot (WB). Immunohistochemistry (IHC) was used to examine the potential of GSK-3β to predict clinical outcome in BC patients. GSK-3β knockdown was achieved using an shRNA plasmid vector in T47D cells. Our research explored the biological reactions and downstream pathways involved. We found excessive GSK-3β expression in BC tissues, which was correlated with worse clinicopathological parameters and clinical outcome. Progression of BC was suppressed by GSK-3β knockdown. Furthermore, suppression of GSK-3β function led to a noticeable decrease in ATP generation, and this was associated with stimulation of AMP-activated protein kinase (AMPK) in T47D cells. Activation of AMPK, a typical sign of autophagy stimulation, was triggered after suppression of GSK-3β function, in parallel with increased generation of LC3 II. Our findings therefore indicate that GSK-3β participates in regulation of migration as well as stimulation of autophagy via mediating activation of the AMPK pathway. This suggests that GSK-3β has potential as a predictor of clinical outcome and as a target for BC therapy.

Key words: GSK-3β; Migration; Autophagy; AMPK; Breast cancer (BC)

Address correspondence to Lu Guo, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, Guangdong 510632, P.R. China. Tel: +86-18169646812; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 495-501, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15331163433914
E-ISSN 1555-3906
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Efficacy Evaluation of Imatinib for the Treatment of Melanoma: Evidence From a Retrospective Study

Xiaoting Wei, Lili Mao, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jie Dai, Xuan Wang, Siming Li, Bixia Tang, Bin LianXieqiao Yan, Xue Bai, Li Zhou, Jun Guo, and Lu Si

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, P.R. China

Melanoma is an aggressive malignancy with a poor prognosis. Current studies show that imatinib treatment is a promising approach in treating advanced melanoma patients harboring
c-Kit mutations or amplifications. We retrospectively analyzed the clinical medical records of 78 patients with metastatic melanoma harboring c-Kit mutations or amplifications. These patients were treated with imatinib at a dose of 400 mg/day continuously unless intolerable toxicities or disease progression occurred. Endpoints for exploration included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease of control rate (DCR). The median OS and PFS of all patients were 13.1 and 4.2 months, respectively. ORR and DCR were 21.8% and 60.3%, respectively. The survival time of patients who achieved partial response or stable disease was significantly superior to those with disease progression. Cox regression analysis showed that patients with M1c stage, subtype of cutaneous melanoma, or elevated LDH level (>upper limit of normal) had higher hazard ratios for overall survival. Our study, combined with those studies targeting patients with a c-Kit alteration, validates the role of imatinib as an important and promising therapeutic agent in the treatment of patients with advanced melanoma.

Key words: Metastatic melanoma; c-Kit aberrations; Imatinib; Efficacy; Progression-free survival (PFS); Overall survival (OS); Response rate

Address correspondence to Lu Si, Deputy Chief Physician, Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, #52 Fucheng Road, Haidian District, Beijing 100142, P.R. China. Tel: +86 01088196348; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 495-501, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15344989701565
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Astragaloside IV Inhibits the Progression of Non-Small Cell Lung Cancer Through the Akt/GSK-3β/β-Catenin Pathway

Liwei Jia,* Dongying Lv,† Shuang Zhang,* Zhenyue Wang*, and Bo Zhou*

*School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, P.R. China
†Heilongjiang Environmental Monitoring Central Station, Harbin, Heilongjiang Province, P.R. China

Astragaloside IV (AS-IV) is an active ingredient in
Astragalus membranaceus and is involved in various biological processes, such as regulating the immune system, and counteracting inflammation and malignancy. The aim of this study was to explore the effect of AS-IV on non-small cell lung cancer (NSCLC) cells. Cell counting kit (CCK)-8 assay and flow cytometry were performed to investigate cell survival and cell death, and Western blotting was performed to assess protein expression. We found that AS-IV inhibited the migration and proliferation of NSCLC cells and caused a noticeable increase in cell death. Furthermore, the expression of Bax, a marker of cell death, was increased, whereas the expression of Bcl-2, an antiapoptotic protein, was reduced. AS-IV also promoted cleavage of caspase-3, another indication of apoptosis. Finally, the Akt/GSK- 3β/β-catenin axis was suppressed in response to AS-IV. Taken together, these findings provide evidence that AS-IV inhibits NSCLC development via inhibition of the Akt/GSK-3β/β-catenin signaling axis. We therefore propose that AS-IV represents a promising novel agent for the treatment of NSCLC.

Key words: Astragaloside IV (AS-IV); Non-small cell lung cancer (NSCLC); Akt; GSK-3β; β-Catenin

Address correspondence to Zhenyue Wang, School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin, Heilongjiang Province 150040, P.R. China. Tel: +86-18256072450; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 509-514, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15278771272963
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Review

The Biological Function of Hepatitis B Virus X Protein in Hepatocellular Carcinoma

Qiaodong Xu,1 Songgang Gu,1 Jiahong Liang, Zhihua Lin, Shaodong Zheng, and Jiang Yan

Department of Biliary-Pancreatic Minimally Invasive Surgery,

The First Affiliated Hospital of Shantou University Medical College, Shantou, P.R. China

Hepatocellular carcinoma (HCC) is one of the major malignant tumors that lead to death. Chronic hepatitis B virus infection is an important risk factor for HCC initiation. HBx protein, encoded by the HBV X gene, is a significant factor that promotes HBV-related HCC, although the exact molecular mechanism remains unclear. This article summarizes the pathological roles and related mechanisms of HBx in HCC. HBx plays a carcinogenic role by promoting cell proliferation, metastasis, and angiogenesis and inhibiting apoptosis in HCC. A detailed study of the biological functions of HBx will help to elucidate the mechanism of hepatocarcinogenesis and lead to the development of novel therapeutic targets for the treatment of HBV-related HCC.

Key words: Hepatocellular carcinoma (HCC); Hepatitis B virus (HBV); Carcinogenic mechanism; Hepatitis B virus X (HBx) protein

1These authors provided equal contribution to this work.
Address correspondence to Jiang Yan, Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, P.R. China. Tel: +86-0754-88905186; Fax: +86-0754-88905186; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it