FBW7 increases chemosensitivity in hepatocellular carcinoma cells through suppression of epithelial-mesenchymal transition

作     者：Jun Yu Wu Zhang Feng Gao Yuan-Xing Liu Zhi-Yun Chen Long-Yu Cheng Shang-Fen Xie Shu-Sen Zheng 

作者机构：Department of Hepatobiliary and Pancreatic Surgerythe First Affiliated HospitalZhejiang University School of Medicine Key Laboratory of MultiOrgan Transplantation of Ministry of Public Health 

出 版 物：《Hepatobiliary & Pancreatic Diseases International》 (国际肝胆胰疾病杂志（英文版）)

年 卷 期：2014年第13卷第2期

页      面：184-191页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from NationalHigh-Tech Research and Development Projects (863 Program)(2012AA021002) Organ Transplantation Key Technology Project(863 Program) (2012AA022409) Zhejiang Province NaturalScience Foundation (LQ12H03002 and LY12H03010) 

主　　题：FBW7 hepatocellular carcinoma doxorubicin epithelial-mesenchymal transition drug resistance 

摘      要：BACKGROUND: FBW7 is a tumor suppressor which regulates a network of proteins with central roles in cell division, cell growth and differentiation. This study aimed to evaluate the role of FBW7in chemosensitivity and epithelial-mesenchymal transition (EMT) in different hepatocellular carcinoma (HCC) cell lines and to investigate the relevant underlying mechanisms.METHODS: Different human HCC cell lines (Hep3B, Huh-7,and SNU-449) were cultured. The cell viability was evaluated by cell counting kit-8, and FBW7 mRNA transcription and protein expression were quantitated by real-time PCR and Western blotting. Expressions of vimentin (mesenchymal biomarker)and E-cadherin (epithelial biomarker) were evaluated by Western blotting and immunocytochemistry. Cell invasion was assayed by Transwell migration, and FBW7 plasmid or siRNA was used to evaluate the effect of FBW7 overexpression or silencing on cell chemosensitivity.RESULTS: FBW7 expression affected tumor cell chemosensitivity to doxorubicin and tumor cell invasive capacity in different HCC cell lines. FBW7hi (high FBW7 expression) Hep3B and FBW7mi (median FBW7 expression) Huh-7 cells were more sensitive to doxorubicin and lower in invasive capacity than FBW7lo (low FBW7 expression) SNU-449 cells. Silencing of FBW7in Huh-7 and Hep3B cells induced the resistance to doxorubicin and enhanced cell invasion, whereas overexpression of FBW7in SNU-449 cells restored the sensitivity to doxorubicin andsignificantly reduced invasive capacity. Furthermore, doxorubicin induced EMT toward mesenchyme in HCC cells. Downregulation of FBW7 in Huh-7 and Hep3B cells or upregulation of FBW7 in SNU-449 cells altered the direction of EMT.CONCLUSIONS: The level of FBW7 expression impacted the tumor resistance to doxorubicin and the invasion capability of HCC cells. FBW7 therefore may be a potential target for the chemotherapy of HCC through the regulation of EMT.