CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro.
Transarterial chemoembolization (TACE) is the standard of care for treatment of intermediate hepatocellular carcinoma (HCC), however, key molecules involved in HCC cell survival and tumor metastasis post-TACE remain unclear. CD147 is a member of the immunoglobulin superfamily that is overexpressed on the surface of HCC cells and is associated with malignant potential and poor prognosis in HCC patients. In this study, using an Earle's Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly increased levels of both apoptosis and autophagy as compared to cells transfected with control siRNA under starvation conditions, whereas no difference was observed between the two treatment groups under normal culture conditions. Furthermore, silencing of CD147 resulted in a remarkable downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in starved SMMC7721 cells. Finally, the combined treatment of starvation and anti-CD147 monoclonal antibody exhibited a synergistic HCC cell killing effect. Our study suggests that upregulation of CD147 under starvation may reduce hepatoma cell death by modulating both apoptosis and autophagy through mTOR signaling, and that CD147 may be a novel potential molecular target to improve the efficacy of TACE.
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China. gouxingchun@189.cn.|Yale School of Medicine, Yale University, New Haven, CT, 06510, USA. gouxingchun@189.cn.|College of Medicine, Xi'an Jiaotong University, Xi'an, 710032, China. gouxingchun@189.cn.
Xingchun
X
Gou
Department of Pathology, Sichuan College of Traditional Chinese Medicine, Mianyang, 721000, China.
Xu
X
Tang
Yale School of Medicine, Yale University, New Haven, CT, 06510, USA.
Derek Kai
DK
Kong
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
Xinying
X
He
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
Xingchun
X
Gao
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
Na
N
Guo
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
Zhifang
Z
Hu
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
Zhaohua
Z
Zhao
School of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China. yankechen@126.com.|Yale School of Medicine, Yale University, New Haven, CT, 06510, USA. yankechen@126.com.|College of Medicine, Xi'an Jiaotong University, Xi'an, 710032, China. yankechen@126.com.
Yanke
Y
Chen
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D051926:Basigin / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003470:Culture Media / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; C497886:BSG protein, human; D003470:Culture Media; D034741:RNA, Small Interfering; D051926:Basigin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
Apoptosis; Autophagy; CD147; Transarterial chemoembolization (TACE); mTOR