Mechanism of gemcitabine-induced apoptosis

Seol, Jae-Won; Lee, You-Jin; Kang, Dong-Won; Kang, Hyung-Sub; Kim, Nam-Soo; Kim, In-Shik; Park, Sang-Youel

Korean Journal of Veterinary Research 2005;45(4):495-500.

Jae-Won Seol, You-Jin Lee, Dong-Won Kang, Hyung-Sub Kang, Nam-Soo Kim, In-Shik Kim, Sang-Youel Park

Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University

Gemcitabine의 세포사멸 기전 연구

설재원, 이유진, 강동원, 강형섭, 김남수, 김인식, 박상열

전북대학교 수의과대학, 헬스케어 사업단

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.

Key Words: apoptosis, A549, caspase, gemcitabine