@article{APS4510,
author = {Yan-qiu Ou and Wen-bo Zhu and Yan Li and Peng-xin Qiu and Yi-jun Huang and Jun Xie and Song-min He and Xiao-ke Zheng and Tian-dong Leng and Dong Xu and Guang-mei Yan},
title = {Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity},
journal = {Acta Pharmacologica Sinica},
volume = {31},
number = {1},
year = {2016},
keywords = {},
abstract = {Aim: To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells.
Methods: Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein level for cyclin D1 and Bcl-2.
Results: Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G1 phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3β activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1.
Conclusion: Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3β and its downstream gene products.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4510}
}