Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells

被引：164

作者：

Guo, Xian-ling ^{[1
,2
]}

Li, Ding ^{[1
]}

Hu, Fei ^{[1
]}

Song, Jian-rui ^{[1
]}

Zhang, Shan-shan ^{[1
]}

Deng, Wei-jie ^{[1
]}

Sun, Kai ^{[1
]}

Zhao, Qiu-dong ^{[1
]}

Xie, Xu-qin ^{[1
]}

Song, Yu-jiao ^{[1
]}

Wu, Meng-chao ^{[1
]}

Wei, Li-xin ^{[1
]}

机构：

[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, Shanghai 200438, Peoples R China

[2] Hang Zhou Sanitarium Navy, Hangzhou, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2012年 / 320卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Autophagy; Hepatocarcinoma; Chemotherapy; Apoptosis; Proliferation; HEPATOCELLULAR-CARCINOMA; CANCER CELLS; DEATH; DELAYS; CONTRIBUTES; PROGRESSION; SURVIVAL; PROTEIN;

D O I：

10.1016/j.canlet.2012.03.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Induction of cell death and inhibition of cell growth are the main targets of cancer therapy. Here we evaluated the role of autophagy on chemoresistance of human hepatocarcinoma (HCC) cell lines, focusing on its crosstalk with cell apoptosis and proliferation. In this study, a chemotherapeutic agent (cisplatin or 5FU) induced the formation of autophagosomes in three human HCC cell lines and upregulated the expression of autophagy protein LC3-II. Inhibition of autophagy by 3-methyladenine or si-beclin 1 increased chemotherapy-induced apoptosis in HCC cells. Meanwhile, increased damage of the mitochondrial membrane potential was also observed in HCC cells when autophagy was inhibited. Furthermore, inhibition of autophagy reduced clone formation and impaired cell growth of HCC cells when treated with chemotherapy. Co-administration of an autophagy inhibitor (chloroquine) and chemotherapy significantly inhibited tumor growth in a mouse xenograft tumor model, with greater extent of apoptosis and impaired proliferation of tumor cells. This study suggests that autophagy is a potential novel target to improve therapy efficiency of conventional chemotherapeutics towards HCC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：171 / 179

页数：9

共 40 条

[1] Autophagy delays apoptotic death in breast cancer cells following DNA damage [J].