Aspirin increases the efficacy of gemcitabine in pancreatic cancer by modulating the PI3K/AKT/mTOR signaling pathway and reversing epithelial‑mesenchymal transition

阿司匹林通过调节 PI3K/AKT/mTOR 信号通路和逆转上皮间质转化来增强吉西他滨对胰腺癌的疗效

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作者:Hanyu Zhou, Xiao Yun, Yongqian Shu, Kequn Xu

Abstract

Gemcitabine is regarded as a standard medication for patients with pancreatic cancer. The aim of the present study was to investigate the impact of aspirin (ASA) on the efficacy of gemcitabine in pancreatic cancer and the potential mechanism. The SW1990 and BxPC-3 human pancreatic cell lines were treated with 2 mmol/l ASA and/or 1 mg/l gemcitabine. The effects of the treatments were tested on the viability, migration and invasion of the cells using MTT, wound healing and Transwell invasion assays. In addition, cell apoptosis was evaluated via flow cytometry with Annexin V-FITC/PI and the western blotting of Bax and Bcl-2. The expression of epithelial-mesenchymal transition (EMT)-associated proteins and activation of the PI3K/AKT/mTOR pathway were also assessed using western blotting. The results reveal that ASA increased the efficacy of gemcitabine in reducing the proliferation, migration and invasion of pancreatic cancer cells and increasing their apoptosis. These effects are associated with inhibition of the PI3K/AKT/mTOR pathway and the reversal of EMT. Thus, the combined use of ASA and gemcitabine is suggested to be a potential therapeutic strategy for patients with pancreatic cancer.

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