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Mechanism of gemcitabine-induced apoptosis  

Seol, Jae-Won (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Lee, You-Jin (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Kang, Dong-Won (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Kang, Hyung-Sub (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Kim, Nam-Soo (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Kim, In-Shik (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Park, Sang-Youel (Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University)
Publication Information
Korean Journal of Veterinary Research / v.45, no.4, 2005 , pp. 495-500 More about this Journal
Abstract
The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.
Keywords
apoptosis; A549; caspase; gemcitabine;
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