Original Article

Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity

Yan-qiu Ou, Wen-bo Zhu, Yan Li, Peng-xin Qiu, Yi-jun Huang, Jun Xie, Song-min He, Xiao-ke Zheng, Tian-dong Leng, Dong Xu, Guang-mei Yan
DOI: 10.1038/aps.2009.172


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.

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