TY - JOUR AU - Ou Yan-qiu AU - Zhu Wen-bo AU - Li Yan AU - Qiu Peng-xin AU - Huang Yi-jun AU - Xie Jun AU - He Song-min AU - Zheng Xiao-ke AU - Leng Tian-dong AU - Xu Dong AU - Yan Guang-mei PY - 2016 TI - Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity JF - Acta Pharmacologica Sinica; Vol 31, No 1 (January 2010): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - 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 G 1 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. UR - http://www.chinaphar.com/article/view/4510