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

Xian Ling Guo, Ding Li, Fei Hu, Jian Rui Song, Shan Shan Zhang, Wei Jie Deng, Kai Sun, Qiu Dong Zhao, Xu Qin Xie, Yu Jiao Song, Meng Chao Wu, Li Xin Wei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalCancer Letters
Volume320
Issue number2
DOIs
Publication statusPublished - 28 Jul 2012
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Chemotherapy
  • Hepatocarcinoma
  • Proliferation

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