Gemcitabine의 세포사멸 기전 연구

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.