ADAM10 overexpression confers resistance to doxorubicin-induced apoptosis in hepatocellular carcinoma.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Cheng-lin YangGui-xing Jiang

Abstract

Chemoresistance represents a major obstacle to successful treatment of hepatocellular carcinoma (HCC). A disintegrin and metalloproteinase 10 (ADAM10) is known to be frequently upregulated in many cancers. We aimed to determine the biological function of ADAM10 in the chemoresistance of HCC cells. Overexpression of ADAM10 in three HCC cell lines (HepG2, Hep3B, and Huh7) conferred protection against doxorubicin-induced apoptosis, as determined by Annexin V staining. Western blot analysis revealed that ADAM10-overexpressing cells had a significantly lower amount of cleaved caspase-3 and an elevated expression of myeloid cell leukemia-1 (Mcl-1), a prosurvival member of the Bcl-2 family. Conversely, RNA interference-mediated silencing of endogenous ADAM10 potentiated doxorubicin-induced apoptosis in HepG2 and Hep3B cells, which was coupled with increased cleavage of caspase-3 and decreased expression of Mcl-1. Ectopic expression of ADAM10 resulted in a marked increase in the phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and Akt. Most interestingly, the pretreatment with the PI3-K inhibitor LY294002 significantly enhanced doxorubicin-induced apoptosis and diminished the Mcl-1 expression in ADAM10-overexpressing Huh7 cells...Continue Reading

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Citations

Dec 20, 2013·Fibrogenesis & Tissue Repair·Krista Rombouts, Vinicio Carloni
Aug 15, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xin TianYouhong Jiang
Mar 22, 2016·Hepatic Oncology·Josiah Cox, Steven Weinman
Jan 16, 2013·Cell Biology International·Weifeng ZhangJianxing He
Aug 3, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lijie YuanXinghan Liu
Dec 11, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xuejun YangLiming Wang
Jun 18, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lin FuEnhua Wang
May 5, 2020·Oncoimmunology·Jacob J OrmeHaidong Dong
Oct 18, 2014·Molecular Medicine Reports·Songyang LiuGuangyi Wang
Nov 21, 2017·Molecular Medicine Reports·Xiancai GeQin Zhang

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