Mechanism of gemcitabine-induced apoptosis

Gemcitabine의 세포사멸 기전 연구

  • 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)
  • 설재원 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 이유진 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 강동원 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 강형섭 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 김남수 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 김인식 (전북대학교 수의과대학, 헬스케어 사업단) ;
  • 박상열 (전북대학교 수의과대학, 헬스케어 사업단)
  • Accepted : 2005.08.18
  • Published : 2005.12.29

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.

Acknowledgement

Supported by : 헬스케어기술개발사업단, 한국과학재단

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