GSK343 induces autophagy and downregulates the AKT/mTOR signaling pathway in pancreatic cancer cells
GSK343 induces autophagy and downregulates the AKT/mTOR signaling pathway in pancreatic cancer cells
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GSK343 诱导胰腺癌细胞自噬并下调 AKT/mTOR 信号通路
DOI：
10.3892/etm.2019.7845
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发表时间：
2019-08
影响因子：
2.7
通讯作者：
Wang W.
中科院分区：
文献类型：
--
作者：
Xu H.;Zhang L.;Qian X.;Zhou X.;Yan Y.;Zhou J.;Ge W.;Albahde M.;Wang W.
胰腺癌是一种常见的恶性肿瘤，预后差，治疗选择有限。zeste增强子同源物2（EZH 2）在不同类型的癌症的进展中起关键作用。在本研究中评估了GSK 343（EZH 2的竞争性抑制剂）对胰腺癌细胞的作用。使用MTT和细胞计数试剂盒-8测定法在AsPC-1和PANC-1细胞中评价细胞活力。还进行流式细胞术和EdU测定以评估GSK 343对细胞增殖、凋亡和细胞周期的影响。利用荧光显微镜和蛋白质印迹分析研究了自噬的诱导和相关的分子机制。结果表明，GSK 343以剂量和时间依赖性方式抑制细胞活力。此外，GSK 343抑制细胞增殖，促进细胞凋亡，并将细胞周期进程阻滞在G1期。此外，GSK 343通过AKT/mTOR信号通路诱导胰腺癌中的自噬。总之，GSK 343对胰腺癌细胞表现出抗癌作用，下调AKT/mTOR信号通路。
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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DOI：
10.1146/annurev.pathol.3.121806.154305
发表时间：
2021-08
期刊：
Annual review of pathology
影响因子：
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作者：
A. Maitra;R. Hruban
通讯作者：
A. Maitra;R. Hruban
影响因子：
21.3
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DOI：
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2008-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
Ougolkov AV;Bilim VN;Billadeau DD
通讯作者：
Billadeau DD
影响因子：
5.7
作者：
Jones BA;Varambally S;Arend RC
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DOI：
10.5194/angeo-2018-92-rc2
发表时间：
2018-10
期刊：
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影响因子：
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作者：
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通讯作者：
Anonymous