期刊
AUTOPHAGY
卷 5, 期 8, 页码 1131-1144出版社
LANDES BIOSCIENCE
DOI: 10.4161/auto.5.8.9996
关键词
hepatocellular carcinoma; hypoxia; chemoresistance; apoptosis; autophagy
类别
资金
- National Natural Science Foundation of China [30700981, 30801347, 30870974]
- Shanghai Science and Technology Committee [045407047, 08XD14003]
- National Key Sci-Tech Special Project of China [2008ZX10002-019, 2008ZX10002-025]
- National Program on Key Basic Research Project [2010CB945600]
- CAS [KSCX1-YW-22]
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.
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