GSK343 induces autophagy and downregulates the AKT/mTOR signaling pathway in pancreatic cancer cells

GSK343 诱导胰腺癌细胞自噬并下调 AKT/mTOR 信号通路

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作者:Hao Xu, Linshi Zhang, Xiaohui Qian, Xiaohu Zhou, Yingcai Yan, Jiarong Zhou, Wenhao Ge, Mugahed Albahde, Weilin Wang

Abstract

Pancreatic cancer is a common malignancy that has a poor prognosis and limited therapeutic options. Enhancer of zeste homolog 2 (EZH2) serves a key role in the progression of different types of cancers. The effect of GSK343 (a competitive inhibitor of EZH2) on pancreatic cancer cells was assessed in the present study. Cell viability was evaluated using MTT and cell counting kit-8 assays in AsPC-1 and PANC-1 cells. Flow cytometry and an EdU assay were also performed to assess the effects of GSK343 on cell proliferation, apoptosis and the cell cycle. The induction of autophagy and associated molecular mechanisms were studied using fluorescence microscopy and western blot analysis. The results demonstrated that GSK343 inhibited cell viability in a dose- and time-dependent manner. Furthermore, GSK343 suppressed cell proliferation, promoted apoptosis and blocked cell cycle progression at the G1-phase. Furthermore, GSK343 induced autophagy in pancreatic cancer via the AKT/mTOR signaling pathway. In conclusion, GSK343 exhibited an anti-cancer effect on pancreatic cancer cells, downregulating the AKT/mTOR signaling pathway.

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