Neoplasma Vol.61, No.2, p.186-192, 2014
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| Title: Autophagy inhibition enhances pan-Bcl-2 inhibitor AT-101-induced apoptosis in non-small cell lung cancer |
| Author: H. MEI, Z. LIN, Y. WANG, G. WU, Y. SONG |
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Abstract: Overexpression of anti-apoptotic Bcl-2 proteins is commonly observed in a variety of cancers and associated with resistance to conventional chemotherapeutic drugs. Targeting multiple anti-apoptotic proteins is now possible with the small molecule BH3 domain mimetics such as AT-101. Autophagy has been found to function as a resistance mechanism against apoptotic cell death. In this study, we investigated the role of autophagy in the AT-101-induced apoptotic death of human lung cancer cells. It was found that AT-101 dose-dependently induced both apoptosis and autophagy in A549 lung cancer cells. And the apoptotic cell death induced by AT-101 was greatly enhanced after autophagy inhibition. Our findings demonstrated that AT-101-induced autophagy was cytoprotective rather than being part of cell death process in lung cancer cells. Inhibition of autophagy in combination with efforts to enhance apoptosis through targeting the Bcl-2 family of proteins may be a promising strategy to overcome drug resistance.
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| Keywords: apoptosis, autophagy, BH3, lung cancer |
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Published online: 02-Dec-2013
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| Year: 2014, Volume: 61, Issue: 2 |
Page From: 186, Page To: 192 |
doi:10.4149/neo_2014_024
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