Journal
ONCOLOGY REPORTS
Volume 31, Issue 2, Pages 649-656Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2013.2890
Keywords
AZD8055; autophagy; hepatocellular carcinoma; AMPK
Categories
Funding
- Science and Technology Program of Guangdong Province [2008B030301028]
- Science and Technology Innovation Fund of Guangdong Medical College [STIF201107]
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AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in several types of cancer cells in vitro and in vivo. However, the effect of AZD8055 on hepatocellular carcinoma (HCC) cells has not been studied. We report that AZD8055 inhibits cell proliferation and colony formation of Hep3B and Huh7 cells but does not cause PARP cleavage, or caspase activation, suggesting that classical apoptosis is not its main mechanism of cell death. By contrast, AZD8055-induced cell death was associated with several characteristics of autophagy, including an increase in acidic vesicular organelle content, conversion of cytosolic LC3-I to membrane-bound LC3-II and elevation of the levels of Atg-5/12, BECN1 and LC3-II. Inhibition of autophagy by 3-methyladenine (3-MA) partially inhibited AZD8055-induced cell death. Furthermore, AZD8055 caused the activation of AMPK and co-treatment with the AMPK inhibitor dorsomorphin also caused a partial but significant reduction of AZD8055-induced cell death. In conclusion, AZD8055-induced HCC cell death is associated with induction of autophagy and activation of AMPK.
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