Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells

Song Jianrui, Qu Zengqiang, Guo Xianling, Zhao Qiudong, Zhao Xue, Gao Lu, Sun Kai, Shen Feng, Wu Mengchao, Wei Lixin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)

Abstract

Hypoxia commonly exists in solid tumors. Under such adverse conditions, adaptive responses including autophagy are usually provoked to promote cell survival. In our study, autophagy, a lysosomal-mediated degradation pathway, is demonstrated as a protective way to make hepatocellular carcinoma cells resistant to chemotherapy under hypoxia. Compared with normoxia, chemotherapeutic agent-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. However, when autophagy was inhibited by 3-MA or siRNA targeted Beclin 1, this reduction was reversed, i.e., chemoresistance was attenuated, which means autophagy mediates the chemoresistance under hypoxia. In conclusion, autophagy decreases hepatoma cells sensitization to chemotherapeutic agents by affecting their apoptotic potential.

Original languageEnglish
Pages (from-to)1131-1144
Number of pages14
JournalAutophagy
Volume5
Issue number8
DOIs
Publication statusPublished - 16 Nov 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Chemoresistance
  • Hepatocellular carcinoma
  • Hypoxia

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