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Autophagy in hypoxia protects cancer cells against apoptosis induced by nutrient deprivation through a Beclin1-dependent way in hepatocellular carcinoma.
MedLine Citation:
PMID:  21769915     Owner:  NLM     Status:  Publisher    
Oxygen deficiency and nutrient deprivation widely exists in solid tumors because of the poor blood supply. However, cancer cells can survive this adverse condition and proliferate continuously to develop. To figure out the way to survive, we investigated the role of autophagy in the microenvironment in hepatocellular carcinoma. In order to simulate the tumor microenvironment more veritably, cells were cultured in oxygen-nutrient-deprived condition following a hypoxia preconditioning. As a result, cell death under hypoxia plus nutrient deprivation was much less than that under nutrient deprivation only. And the decreased cell death mainly attributed to the decreased apoptosis. GFP-LC3 and electron microscopy analysis showed that autophagy was significantly activated in the period of hypoxia preconditioning. However, inhibited autophagy by autophagic inhibitor-3-MA significantly abrogated the apoptosis reduction in hypoxia, which implied the involvement of autophagy in protection of hepatocellular carcinoma cells against apoptosis induced by starvation. Furthermore, Beclin 1 was proved to play an important role in this process. siRNA targeted Beclin 1 was transfected into hepatocellular carcinoma cells. And both data from western blot detecting the expression of LC3II and from transmission microscopy observing the accumulation of autophagosomes showed that autophagy was inhibited obviously as a result of Beclin 1 knockdown. Besides, the decreased apoptosis of starved cells under hypoxia was reversed. Taken together, these results suggest that autophagy activated by hypoxia mediates the tolerance of hepatocellular carcinoma cells to nutrient deprivation, and this tolerance is dependent on the activity of Beclin 1. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
Jianrui Song; Xianling Guo; Xuqin Xie; Xue Zhao; Ding Li; Weijie Deng; Yujiao Song; Feng Shen; Mengchao Wu; Lixin Wei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-18
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  -     ISSN:  1097-4644     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
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