World Journal of Surgical Oncology | |
pERK1/2 silencing sensitizes pancreatic cancer BXPC-3 cell to gemcitabine-induced apoptosis via regulating Bax and Bcl-2 expression | |
Dong Chen1  Guangzhen Ni2  Zimin Liu1  Fengyun Hao2  Xueguang Dong3  Xingjiao Lu4  Min Wang3  | |
[1] Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China;Department of Clinical Laboratory, People’s Hospital of Weifang, Weifang, Shangdong, China;Department of Clinical Laboratory, People’s Hospital of Laiwu, Laiwu, Shangdong, China;Department of Internal Neurology, People’s Hospital of Zhangqiu, ZhangQiu, Shangdong, China | |
关键词: Gemcitabine; Bax; Bcl-2; ERK1/2; Pancreatic cancer; | |
Others : 1131010 DOI : 10.1186/s12957-015-0451-7 |
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received in 2014-07-03, accepted in 2015-01-08, 发布年份 2015 | |
【 摘 要 】
Background
Our previous study has demonstrated that knockdown of activated ERK1/2(pERK1/2) sensitizes pancreatic cancer cells to chemotherapeutic drug gemcitabine (Gem) treatment. However, the details of this survival mechanism remain undefined. It has also shown that Bcl-2 confers resistance and Bax sensitizes to gemcitabine-induced apoptosis in pancreatic cancer cells. Furthermore, the extracellular signaling-regulated kinase (ERK) signaling pathway regulates Bcl-2/Bax expression ratio. We therefore tested the hypothesis that pancreatic cancer cells are resistant to gemcitabine and this resistance is due to activation of ERK1/2 and subsequent upregulation of Bcl-2 and downregulation of Bax.
Methods
Pancreatic cancer cell BXPC-3 was used in the study. The effect of pharmacological inhibition of ERK1/2 on resistance of pancreatic cancer cells to apoptosis induced by treatment with gemcitabine was analyzed. The following methods were utilized: TUNEL and ELISA were used to detect apoptosis. Western blot was used to detect the protein expression.
Results
Gemcitabine treatment enhanced the activity of ERK1/2 in the BXPC-3 cells. Inhibition of the ERK1/2 by PD98059 could downregulate Bcl-2 and upregulate Bax and was associated with restoration of sensitivity to gemcitabine in BXPC-3 cells. Depletion of endogenous Bcl-2 expression by specific small interfering RNA transfection significantly increased gemcitabine-induced cell apoptosis. Combined treatment with PD98059 and Bax siRNA transfection could decrease gemcitabine-induced ERK1/2 and Bax activation, which subsequently resulted in decreased apoptosis.
Conclusions
The upregulation of ERK1/2-dependent Bcl-2 and downregulation of ERK1/2-dependent Bax can protect human pancreatic cancer cells from gemcitabine-induced apoptosis. Targeting the ERK1/2-Bax/Bcl-2 pathway may in part lead to sensitization of pancreatic cancer to gemcitabine.
【 授权许可】
2015 Wang et al.; licensee BioMed Central.
【 预 览 】
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