BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer
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- 作者：Li Jiang (10) (9)
Man Luo (9)
Dan Liu (9)
Bojiang Chen (9)
Wen Zhang (9)
Lin Mai (9)
Jing Zeng (9)
Na Huang (11)
Yi Huang (12)
Xianming Mo (13)
Weimin Li (9) - 关键词：BAD protein ; Non ; small cell lung cancer ; Apoptosis ; Cell proliferation ; Overexpression
- 刊名：Cancer Cell International
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：13
- 期：1
- 全文大小：1563KB
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32. Cekanova M, Fernando R, Wimalasena J: / P1鈥?2鈥?1: the BCL2 antagonist of death, BAD is down-regulated in breast cancer and inhibits cancer cell invasion. Abstracts: Thirty-Fourth Annual CTRC-AACR San Antonio Breast Cancer Symposium; 2011. - 作者单位：Li Jiang (10) (9)
Man Luo (9)
Dan Liu (9)
Bojiang Chen (9)
Wen Zhang (9)
Lin Mai (9)
Jing Zeng (9)
Na Huang (11)
Yi Huang (12)
Xianming Mo (13)
Weimin Li (9)
10. Department of Respiratory Medicine, Nanchong Central Hospital, Nanchong, 637000, P.R China
9. Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, P.R China
11. Department of Respiratory Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu, 610072, P.R China
12. Clinical Laboratory Department, Sichuan Academy of Medical Sciences and Sichuan Provincial People鈥檚 Hospital, Chengdu, 610072, P.R China
13. Laboratory Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P.R China
文摘
Background The pro-apoptotic Bcl-2 protein BAD initiated apoptosis in human cells and has been identified as a prognostic marker in non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functions of BAD in NSCLC. Methods Overexpression of BAD was performed by transfecting different NSCLC cell lines with wild-type BAD. Cell proliferation, cell cycle, apoptosis, and invasion were characterized in vitro. Tumorigenicity was analyzed in vivo. Western blot was performed to determine the effects of BAD overexpression on the Bcl-2 family proteins and apoptosis-related proteins. Results Overexpression of BAD significantly inhibited cell proliferation in H1299, H292, and SPC-A1 but not in SK-MES-1 and H460 cell lines in vitro. BAD overexpression also reduced the tumorigenicity of H1299/SPC-A1 cell in vivo. However, no appreciable effects on cell cycle distribution and invasion were observed in all these cell lines. BAD overexpression also induced apoptosis in all cell types, in which process expression of mitochondrial cytochrom c (cyto-c) and caspase 3 were increased, whereas Bcl-xl, Bcl-2, Bax and caspase 8 expressions did not changed. These findings indicated that a mitochondrial pathway, in which process cyto-c was released from mitochondrial to activate caspase 3, was involved in BAD overexpression-mediated apoptosis. Conclusions Our data suggested that increased expression of BAD enhance apoptosis and has negative influence on cell proliferation and tumor growth in NSCLC. Bad is a new potential target for tumor interventions.