Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin  

作　　者：SHEN Bo CHEN Haibin ZHOU Hongguang WU Mianhua 

机构地区：[1]Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine,Nanjing 210014,China [2]Science and Technology Department,Nanjing University of Chinese Medicine,Nanjing 210023,China [3]The First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China

出　　处：《Journal of Traditional Chinese Medicine》2021年第3期381-389,共9页中医杂志（英文版）

基　　金：Supported by Nanjing Medical Science and technique Development Foundation (No.QRX17194)。

摘　　要：OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma(HCC) cells in vitro and in vivo and to propose a mechanism of action.METHODS: A human Hep G2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability.Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin(mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology.RESULTS: Celastrol decreased the viability of Hep G2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in Hep G2 cells. Moreover,celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis(up-regulation of cleaved-caspase-3,-8,-9, and cleaved-PARP) and inhibited the activation of mTOR in vivo.CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.

关 键 词：MTOR CARCINOMA HEPATOCELLULAR apoptosis CASPASES CELASTROL 

分 类 号：R735.7[医药卫生—肿瘤]