Oncology Research 24(6) Abstracts

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Oncology Research, Vol. 24, pp. 391-398, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14666990347518
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
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miR-489 Suppresses Proliferation and Invasion of Human Bladder Cancer Cells

Jing Li, Weixing Qu, Yazhou Jiang, Yi Sun, Yongyi Cheng, Tiejun Zou, and Shuangkuan Du

Department of Urology, Shaanxi Provincial People’s Hospital, Xi’an, China

MicroRNAs (miRNAs) have been shown to be involved in bladder cancer progression. miR-489 (also known as miR-489-3p) was recently reported to be a tumor suppressor in several cancers. However, its exact role and mechanism in the progression of bladder cancer are largely unknown. In this study, we explore the role of miR-489 in the proliferation and invasion of human bladder cancer cells. The miR-489 expression levels were detected in bladder cancer and normal adjacent tissues, as well as in human normal bladder epithelial cells and bladder cancer cell lines. The results showed that miR-489 was sharply reduced in bladder cancer tissues and cell lines. Then the miR-489 mimic or oligo anta-miR-489 was transfected into T24 and UMUC3 bladder cancer cell lines. The results showed that the miR-489 mimic greatly increased the miR-489 level and significantly decreased the proliferation and invasion of T24 and UMUC3 cells. In contrast, the anta-miR-489 had a completely opposite effect on miR-489 expression, cell proliferation, and cell invasion. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-489 targeted the mRNA 3
ʹ-untranslated region (3ʹ-UTR) region of Jagged1 (JAG1), a Notch ligand. In conclusion, miR-489 suppressed proliferation and invasion of human bladder cancer cells.

Key words: miR-489; Bladder cancer; Proliferation; Invasion; JAG1

Address correspondence to Jing Li, Ph.D., Department of Urology, Shaanxi Provincial People’s Hospital, No. 256, Youyi West Road, Xi’an 710068, China. Tel: +86-29-85251331; Fax: +86-29-85251331; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 399-404, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103239
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
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miR-183 Modulates Cell Apoptosis and Proliferation in Tongue Squamous Cell Carcinoma SCC25 Cell Line

Dayong Yan,*1 Xiaoqing Cai,*1 and Yu Feng†

*Oral and Maxillofacial Surgery, The Central Hospital of Zhengzhou, University of Zhengzhou, Zhengzhou, Henan, P.R. China
†Anesthesia Medicine, The Central Hospital of Zhengzhou, University of Zhengzhou, Zhengzhou, Henan, P.R. China

This study was designed to investigate the role of miR-183 in modulating cell growth and apoptosis of tongue squamous cell carcinoma SCC25 cell line. Human squamous epithelial cell and squamous cell carcinoma cell line SCC25 was used, and miR-183 was inhibited. Cell growth, colony formation, and apoptotic rate, as well as the expression of caspase 3 and BCL-xL, were detected. Results showed that miR-183 was significantly overexpressed in the SCC25 cell line when compared with normal control. The miR-183 inhibitor reduced cell growth and colony formation, while the apoptosis percentage was significantly increased. The expression of activated caspase 3 and BCL-xL was obviously up- and downregulated in siRNA-transfected cells, respectively. In conclusion, miR-183 contributed to cell growth and proliferation, and suppressed cell apoptosis in SCC25 cells. Therefore, miR-183 might serve as a therapeutic target in tongue squamous cell carcinoma (TSCC).

Key words: Tongue squamous cell carcinoma (TSCC); miR-183; Cell proliferation; Apoptosis; SCC25 cells

1These authors provided equal contribution to this work.
Address correspondence to Xiaoqing Cai, Oral and Maxillofacial Surgery, The Central Hospital of Zhengzhou, University of Zhengzhou, No. 195 Tongbai Road, Zhengzhou 450007, Henan, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 405-413, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103437
E-ISSN 1555-3906
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MicroRNA-223 Promotes Tumor Progression in Lung Cancer A549 Cells via Activation of the NF-κB Signaling Pathway

Li Huang, Fang Li, Pengbo Deng, and Chengping Hu

Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

Our study aimed to investigate the role of microRNA-223 (miR-223) in lung cancer A549 cells and to further elucidate its possible regulatory mechanism. The expression levels of normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549 were investigated by quantitative real-time PCR. The A549 cells were transfected with miR-223 inhibitor and miR-223 scramble. Afterward, the effects of miR-223 inhibition on cell viability, invasion, and apoptosis, as well as the expression levels of nuclear factor-
κB (NF-κB) and its downstream proteins, were detected. In addition, the NF-κB inhibitor JSH-23 was used to detect the relationship between NF-κB and miR-223. miR-223 was upregulated in human lung cancer A549 cells when compared with BEAS-2B cells. In addition, miR-223 expression was successfully inhibited by the miR-223 inhibitor. Suppression of miR-223 significantly decreased cell viability, inhibited invasion, and induced apoptosis of lung cancer A549 cells. Suppression of miR-223 resulted in a significant decrease in the expression levels of NF-κB and its downstream proteins P-IKBα and P-IKKα/β. After treatment with the NF-κB inhibitor, the inhibitory effects of miR-233 inhibitor on cell invasion, as well as the expression levels of NF-κB and p-p65, were enhanced. Our findings indicate that miR-223 may increase proliferation, promote invasion, and inhibit apoptosis of lung cancer A549 cells via activation of the NF-κB signaling pathway. miR-223 may serve as a potential therapeutic target in lung cancer.

Key words: Lung cancer; MicroRNA-223 (miR-223); Cell proliferation; Cell apoptosis; Cell invasion; NF-κB signal pathway

Address correspondence to Chengping Hu, Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China. Tel: +8615201291971; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 415-427, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103473
E-ISSN 1555-3906
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MicroRNA-155 Downregulation Promotes Cell Cycle Arrest and Apoptosis in Diffuse Large B-Cell Lymphoma

Fu-qiang Zhu,*1 Li Zeng,†1 Na Tang,* Ya-ping Tang,‡ Bo-ping Zhou,* Fang-fang Li,* Wei-gang Wu,* Xiao-bing Zeng,* and Shu-song Peng*

*Department of Pathology, the Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, P.R. China
†Department of Gastroenterology, the First Affiliated Hospital of Shenzhen University, the Second People’s Hospital of Shenzhen, Shenzhen, P.R. China
‡Department of Operation Room of Luohu, Maternity and Child Health Care Hospital of Shenzhen, Shenzhen, P.R. China

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients’ tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-
β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.

Key words: Lymphoma; MicroRNA-155 (miR-155); Transforming growth factor-β receptor 2 (TGFBR2); Cell cycle; Apoptosis

1These authors provided equal contribution to this work.
Address correspondence to Shu-song Peng, Department of Pathology, the Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, East Longguan Road No. 101, Longhua New District, Shenzhen 518020, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 429-435, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103518
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
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MicroRNA-1284 Inhibits Cell Viability and Induces Apoptosis of Ovarian Cancer Cell Line OVCAR3

Changqing Pan, Dan Wang, Yao Zhang, and Wenliang Yu

Department of Obstetrics and Gynecology, Mianyang Central Hospital, Mianyang, Sichuan, P.R. China

Ovarian cancer is a malignancy with high mortality among women. Multiple reports show that microRNAs (miRs) act as regulators in ovarian cancer inhibition, while the role of miR-1284 in ovarian cancer is still unknown. This study aimed to investigate the effects of miR-1284 on ovarian cancer cells. Human ovarian cancer cell line OVCAR3 was cultured and transfected with miR-1284 mimics, inhibitors, or control. Viability and apoptosis of transfected cells were then determined by MTT assay, BrdU assay, and flow cytometry. Expression changes of p27, p21, and PI3K/Akt pathway-related proteins were measured by Western blot. Results showed that miR-1284 overexpression suppressed cell viability while increasing the apoptosis in OVCAR3 cells. Moreover, the expression level of p27 was upregulated by miR-1284 overexpression. Furthermore, miR-1284 overexpression and Akt inhibitor GSK690693 downregulated the levels of p-Akt and Bcl-2 while upregulating the levels of Bax and caspase 3. However, miR-1284 suppression attenuated the regulatory effects of GSK690693 on these proteins. In conclusion, miR-1284 could inhibit cell viability via regulating the expression of p27 and induce apoptosis via regulating the PI3K/Akt pathway in OVCAR3 cells.

Key words: MicroRNA-1284; Ovarian cancer; Cell viability; Apoptosis; PI3K/Akt pathway; p27

Address correspondence to Changqing Pan, Department of Obstetrics and Gynecology, Mianyang Central Hospital, No. 12 Changjia Lane, Jingzhong Street, Mianyang 621000, Sichuan, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 437-445, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14685034103554
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
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Knockdown of SPOCK1 Inhibits the Proliferation and Invasion in Colorectal Cancer Cells by Suppressing the PI3K/Akt Pathway

Ping Zhao,* Hai-Tao Guan,† Zhi-Jun Dai,† Yu-Guang Ma,† Xiao-Xu Liu,† and Xi-Jing Wang†

*Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China
†Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China

Sparc/osteonectincwcv, and kazal-like domains proteoglycan (testican) 1 (SPOCK1), known as testican-1, were found to be involved in the development and progression of tumors. However, in colorectal cancer (CRC), the expression pattern of SPOCK1 and its functional role remain poorly investigated. In the present study, we explored the role of SPOCK1 in CRC. Our results demonstrated that SPOCK1 is overexpressed in CRC cell lines. SPOCK1 silencing significantly inhibited the proliferation in vitro and the tumor growth in vivo. Furthermore, SPOCK1 silencing significantly attenuated the migration/invasion by reversing the EMT process in CRC cells. Finally, knockdown of SPOCK1 obviously decreased the protein expression levels of p-PI3K and p-Akt in HCT116 cells. In total, our study demonstrated for the first time that knockdown of SPOCK1 inhibits the proliferation and invasion in CRC cells, possibly through the PI3K/Akt signaling pathway. Therefore, SPOCK1 may be a potential therapeutic target for the treatment of CRC.

Key words: Sparc/osteonectincwcv, and kazal-like domains proteoglycan (testican) 1 (SPOCK1); Colorectal cancer (CRC); Invasion; PI3K/Akt pathway

Address correspondence to Hai-Tao Guan, Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 West No. 5 Road, Xi’ an, 710004 Shaanxi Province, P.R. China. Tel: +86-029-87678560; Fax: +86-029-87678560; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 447-453, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103590
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
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Astragaloside IV Enhances Cisplatin Chemosensitivity in Human Colorectal Cancer via Regulating NOTCH3

Tao Xie,* Yao Li,† Shi-Lei Li,* and Hai-Feng Luo‡

*Department of General Surgery, Rizhao People’s Hospital, Shandong, P.R. China
†Department of Cardiology, Rizhao People’s Hospital, Shandong, P.R. China
‡Department of General Surgery, The first Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, P.R. China

Although astragaloside IV exhibits anti-inflammation, immunoregulatory, and anticancer properties, the chemosensitization effects of astragaloside IV in colorectal cancer have never been reported. Our study tested whether astragalosidecould increase cisplatin sensitivity in colorectal cancer. CCK-8 assay was used to measure the cell viability of colorectal cancer cells. Quantitative real-time PCR and Western blot were performed to determine the mRNA and protein expression, respectively. Our data revealed that astragaloside IV administration significantly suppressed the cell growth of colorectal cancer cells, whereas no obvious cytotoxicity of astragaloside IV was observed in nonmalignant colonic cells. In addition, combined treatment with astragaloside IV dramatically elevated the chemosensitivity of colorectal cancer cells to cisplatin. Mechanical investigation revealed that the mRNA and protein expression of NOTCH3 was significantly lower in cisplatin and astragaloside IV-treated cells compared with cells treated with cisplatin alone. On the contrary, no obvious changes in tumor cell growth were shown after upregulation of NOTCH3 whether in the presence or absence of astragaloside IV. Thus, our data demonstrate that astragaloside IV increases the chemosensitivity of colorectal cancer cells to cisplatin, at least partly, through inhibition of NOTCH3. This study suggests that combined therapy with astragaloside IV might be a novel therapeutic approach for colorectal cancer.

Key words: Colorectal cancer (CRC); Astragaloside IV; Drug resistance

Address correspondence to Hai-Feng Luo, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning Province, P.R. China Tel: +86-411-83635963-2086; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 455-461, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103635
E-ISSN 1555-3906
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RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells

Gaowu Hu,* Ye Xu,* Wenquan Chen,* Jiandong Wang,† Chunying Zhao,†1 and Ming Wang*1

*Department of General Surgery, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai, P.R. China
†Department of Breast Surgery, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

Breast cancer is a highly prevalent disease affecting women. The association of IQ motif containing GTPase-activating protein 3 (IQGAP3) and breast cancer is poorly defined. Here we reported that IQGAP3 is a key regulator of cell proliferation and metastasis during breast cancer progression. The expression of IQGAP3 was significantly increased in breast tissues compared to nontumor tissues at both protein and mRNA levels. Furthermore, IQGAP3 had a high expression level in ZR-75-30 and BT474 compared to other breast cancer cell lines. Depletion of IQGAP3 through RNA interference in ZR-75-30 and BT474 significantly inhibited cell proliferation. More importantly, IQGAP3 silencing in breast cancer cells notably repressed cell migration and invasion. Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist. Since expression of IQGAP3 seems to be associated with the pathogenesis of breast cancer and suppression of it can inhibit cancer cell growth and metastasis, IQGAP3 may be a potential therapeutic target in human breast cancer.

Key words: IQ motif containing GTPase-activating protein 3 (IQGAP3); Breast cancer; Proliferation; Migration; Invasion

1These authors provided equal contribution to this work.
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: +86-13501844713; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Chunying Zhao, Department of Breast Surgery, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, P.R. China. Tel: +86-18017262879; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 463-475, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103671
E-ISSN 1555-3906
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Inhibition of Proliferation, Migration, and Invasion by Knockdown of Pyruvate Kinase-M2 (PKM2) in Ovarian Cancer SKOV3 and OVCAR3 Cells

Yi Miao,1 Meng Lu,1 Qin Yan, Shuangdi Li, and Youji Feng

Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, Shanghai, P.R. China

Pyruvate kinase (PK) is a key enzyme in the process of glycolysis, catalyzing phosphoenolpyruvate (PEP) into pyruvate. Currently, PK isozyme type M2 (PKM2), one subtype of PK, has been proposed as a new tumor marker with high expression in various tumor tissues. Here we aimed to explore the effects of siRNAPKM2 on ovarian carcinoma (OC) cell lines SKOV3 and OVCAR3, in which PKM2 was notably expressed. PKM2 gene interference lentivirus vectors were built by miRNA transfection assay. siRNA-PKM2-transfected SKOV3 and OVCAR3 cells were evaluated for cell proliferation, cell cycle distribution, cell apoptosis, cell migration, and invasion in this study. In addition, the expression levels of several tumor-related genes were measured using real-time PCR and Western blot. Results showed that siRNA-PKM2 markedly inhibited cell proliferation, induced apoptosis, and caused cell cycle arrest at the G0/G1phase. Cell migration and invasion were significantly suppressed by siRNA-PKM2. Furthermore, the tumor-related genes caspase 7, Bad, and E-cadherin were upregulated, while MMP2, HIF1
a, VEGF, and MMP9 were depressed by siRNA-PKM2. The function of siRNA-PKM2 on the biological behavior of OC cells indicated that PKM2 may also be a target for treatment of OC.

Key words: Pyruvate kinase isozyme type M2 (PKM2); Ovarian carcinoma (OC); Cell proliferation; Metastasis; Signaling pathway

1These authors provided equal contribution to this work.
Address correspondence to Dr. Youji Feng, Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Hongkou District, 200080 Shanghai, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 477-485, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14685034103716
E-ISSN 1555-3906
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Knockdown of Collagen Triple Helix Repeat Containing-1 Inhibits the Proliferation and Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma Cells

Xue-fei Jin, Hai Li, Shi Zong, and Hong-yan Li

Department of Urology, China–Japan Union Hospital of Jilin University, Changchun, P.R. China

Collagen triple helix repeat containing-1 (CTHRC1), a secreted glycoprotein, is frequently upregulated in human cancers. However, the functional role of CTHRC1 in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to explore the role of CTHRC1 in RCC. Our results demonstrated that CTHRC1 was upregulated in RCC tissues and cell lines. Knockdown of CTHRC1 significantly inhibits the proliferation in RCCs. Furthermore, knockdown of CTHRC1 significantly inhibited the epithelial-to-mesenchymal transition (EMT) process in RCCs, as well as suppressed RCC cell migration and invasion. Mechanistically, knockdown of CTHRC1 inhibited the expression of
β-catenin, c-Myc, and cyclin D1 in RCC cells. In conclusion, the results of the present study indicated that CTHRC1 downregulation inhibited proliferation, migration, EMT, and β-catenin expression in RCC cells. Therefore, CTHRC1 may be a potential therapeutic target for the treatment of RCC.

Key words: Collagen triple helix repeat containing-1 (CTHRC1); Renal cell carcinoma (RCC); Invasion; Wnt/β-catenin signaling

Address correspondence to Hong-yan Li, Department of Urology, China–Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. Tel: +86-0431-84995222; Fax: +86-0431-84995222; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 487-494, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14685034103752
E-ISSN 1555-3906
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CSTB Downregulation Promotes Cell Proliferation and Migration and Suppresses Apoptosis in Gastric Cancer SGC-7901 Cell Line

Jian Zhang,*1 ZhenFeng Shi,†1 JinXing Huang,‡ and XiaoGuang Zou§

*Department of Cancer Center, The First People’s Hospital of Kashi Prefecture, Kashi Prefecture, Xinjiang, P.R. China
†Department of Urology Surgery Center, The People’s Hospital of Xinjiang Uyghur Autonomous Region, Xinjiang, P.R. China
‡Department of Urinary Surgery, The People’s Hospital of Shache County, Xinjiang, P.R. China
§The First People’s Hospital of Kashi Prefecture, Xinjiang, P.R. China

This study aimed to investigate the pivotal role of cystatin B (CSTB) in the development of gastric cancer and to explore its possible regulatory mechanism. Human gastric cancer SGC-7901 cells as a model in vitro were transfected with plasmid PCDNA3.1-CSTB and siRNA-CSTB using Lipofectamine 2000. Quantitative realtime PCR (qRT-PCR) and Western blotting were performed to determine the relative expression of CSTB and PI3K/Akt/mTOR pathway-related protein. Moreover, MTT assay, Transwell assay, and flow cytometry were used to assess cell proliferation, migration, and apoptosis, respectively. The results showed that CSTB was significantly downregulated in SGC-7901 cells compared with gastric epithelial cells. CSTB was successfully overexpressed and suppressed after cells were transfected with pc-CSTB and si-CSTB, respectively. Moreover, cell viability and migration were significantly decreased after being transfected with pc-CSTB when compared with the control group, while being obviously increased after transfection with si-CSTB. However, cell apoptosis was significantly induced after being transfected with pc-CSTB, while being obviously suppressed after transfection with si-CSTB. Besides, the expression levels of p-PI3K, p-Akt, and p-mTOR proteins were all significantly decreased in the pc-CSTB transfection group when compared with the control group, while being increased in the si-CSTB transfection group. Our findings suggest that CSTB downregulation may promote the development of gastric cancer by affecting cell proliferation and migration, and the PI3K/Akt/mTOR signaling pathway was activated in this process. CSTB may serve as a potential therapeutic target for gastric cancer.

Key words: Gastric cancer; Cystatin B (CSTB); Proliferation; Migration; Apoptosis; PI3K/Akt/mTOR pathway

1These authors are co-first authors in this study.
Address correspondence to XiaoGuang Zou, The First People’s Hospital of Kashi Prefecture, No. 120 Yingbin Road, Kashi Prefecture, Xinjiang 844000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 495-509, 2016
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DOI: http://dx.doi.org/10.3727/096504016X
14685034103950
E-ISSN 1555-3906
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Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL

Su-Hoon Lee, Suh-Kyung Hyun, Hak-Bong Kim, Chi-Dug Kang, and Sun-Hee Kim

Department of Biochemistry, Pusan National University School of Medicine, Yangsan, South Korea

Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a poor prognosis and high recurrence rate. In the present study, we identified CD133, one of the markers of cancer stem cells, as a novel molecular target of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In four human HCC cell lines established from primary HCC tumors, we found that CD133-high human liver cancer stem-like cells (CD133hi) derived from the SNU-475 cell line were highly susceptible to TRAIL compared to other HCC cell lines with a small population of CD133. CD133hi SNU-475 cells showed upregulation of TRAIL receptor DR5 and stemness-related genes such as c-Myc and ABC transporters compared to their CD133-low (CD133lo) cells. Hypersensitivity of CD133hi cells to TRAIL was associated with c-Myc-mediated upregulation of DR5 and downregulation of c-FLIPL in the cells. Knockdown of CD133 expression in CD133hi cells resulted in the downregulation of c-Myc, and depletion of c-Myc caused a decrease in the cell surface expression of DR5 and an increase in the expression of c-FLIPL and, consequently, attenuated TRAIL-induced cytotoxicity and apoptosis of CD133hi cells. These results suggest that TRAIL may provide a new strategy for CD133hi CSCs of HCC-targeted therapies and, potentially, for therapies of other CD133-expressing types of cancer.

Key words: TRAIL; Hepatocellular carcinoma (HCC); Cancer stem cells; c-Myc; CD133

Address correspondence to Sun-Hee Kim, Department of Biochemistry, #710, Pusan National University School of Medicine, 49 Busandaehak-roMulgeum-eupYangsan-siGyeongsangnam-do 626-870, South Korea. Tel: +82 51 510 8081; Fax: +82 51 510 8086; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Chi-Dug Kang, Department of Biochemistry, #710, Pusan National University School of Medicine, 49 Busandaehak-roMulgeum-eupYangsan-siGyeongsangnam-do 626-870, South Korea. Tel: +82 51 510 8081; Fax: +82 51 510 8086; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 511-519, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14719078133483
E-ISSN 1555-3906
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Knockdown of SLC34A2 Inhibits Hepatocellular Carcinoma Cell Proliferation and Invasion

Yanhua Li,*1 Xia Chen,†1 and Hong Lu*

*Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, P.R. China
†Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, P.R. China

The gene solute carrier family 34 (sodium phosphate), member 2 (
SLC34A2), is a member of the SLC34 family. Increasing evidence suggests that SLC34A2 is involved in the development of many human carcinomas. However, its role in hepatocellular carcinoma (HCC) is still unclear. Therefore, in this study we investigated the role of SLC34A2 in HCC and explored the underlying mechanism. We found that the expression of SLC34A2 is upregulated in HCC cell lines. Knockdown of SLC34A2 obviously inhibited HCC cell proliferation, migration/invasion, and the epithelial–mesenchymal transition (EMT) phenotype. Furthermore, knockdown of SLC34A2 significantly inhibited the expression of phosphorylated PI3K and AKT in HCC cells. Taken together, these results suggest that knockdown of SLC34A2 inhibits proliferation and migration by suppressing activation of the PI3K/AKT signaling pathway in HCC cells, and SLC34A2 may be a potential therapeutic target for the treatment of HCC.

Key words: Hepatocellular carcinoma (HCC); Epithelial–mesenchymal transition (EMT); PI3K/AKT pathway

1These authors provided equal contribution to this work.
Address correspondence to Hong Lu, Department of Oncology, Huaihe Hospital of Henan University, No. 8 of Baobei Road, Kaifeng 475000, P.R. China. Tel: +86-0371-23906821; Fax: +86-0371-23906821; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 521-528, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X
14719078133528
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC.
Printed in the USA. All rights reserved

A Randomized Controlled Open-Label Pilot Study of Simvastatin Addition to Whole-Brain Radiation Therapy in Patients With Brain Metastases

Manal El-Hamamsy,* Hesham Elwakil,† Amr S. Saad,† and May A. Shawki*

*Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
†Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Statins have been reported to have a potential radiosensitizing effect that has not been evaluated in clinical trials. The aim of this study was to evaluate the efficacy and safety of simvastatin in addition to whole-brain radiation therapy (WBRT) in patients with brain metastases (BM). A prospective randomized, controlled, open-label pilot study was conducted on 50 Egyptian patients with BM who were randomly assigned to receive 30-Gy WBRT (control group: 25 patients) or 30 Gy WBRT + simvastatin 80 mg/day for the WBRT period (simvastatin group: 25 patients). The primary outcome was radiological response at 4 weeks after WBRT. Secondary outcomes were 1-year progression-free survival (PFS), 1-year overall survival (OS), and health-related quality of life (HRQL) that was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and its brain module (BN-20), at baseline, after WBRT, and 4 weeks after WBRT. The addition of simvastatin was tolerated. Twenty-one patients were not evaluated for radiological response because of death (
n = 16), noncompliance to follow-up (n = 4), and clinical deterioration (n = 1). Response rates were 60% and 78.6% (p = 0.427), 1-year PFS rates were 5.2% and 17.7% (p = 0.392), and 1-year OS rates were 12% and 8% (p = 0.880) for the control group and simvastatin group, respectively. Nonsignificant differences were found between the two arms regarding HRQL scales. The addition of simvastatin 80 mg/day did not improve the clinical outcomes of patients with BM receiving WBRT.

Key words: Brain metastases (BM); Quality of life; Simvastatin; Whole-brain radiation therapy (WBRT)

Address correspondence to May A. Shawki, M.Sc., Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Street of “African Union Organization” beside the Ain Shams University Specialized Hospital, Abbaseya, Cairo 1566, Egypt.