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In vitro comparative studies of resveratrol and triacetylresveratrol on cell proliferation apoptosis and STAT3 and NFκB signaling in pancreatic cancer cells

机译:白藜芦醇和三乙酰基白藜芦醇对胰腺癌细胞增殖凋亡以及STAT3和NFκB信号传导的体外比较研究

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摘要

Resveratrol (RES) has been studied extensively as an anticancer agent. However, the anticancer effects of triacetylresveratrol (TRES, an acetylated analog of RES) which has higher bioavailability have not been well established. We comparatively evaluated their effects on cell proliferation, apoptosis and the molecular changes in STAT3, NFκB and apoptotic signaling pathways in pancreatic cancer cells. Apoptosis was determined by flow cytometry. The nuclear translocation and interaction of STAT3 and NFκB were detected by Western blotting and immunoprecipitation, respectively. Both TRES and RES inhibited cell viability, and induced apoptosis of pancreatic cancer cells in a concentration and incubation time-dependent manner. TRES, similarly to RES, inhibited the phosphorylation of STAT3 and NFκB, down-regulated Mcl-1, and up-regulated Bim and Puma in pancreatic cancer cells. Remarkably, we, for the first time, observed that both TRES and RES suppressed the nuclear translocation, and interrupted the interaction of STAT3 and NFκB in PANC-1 cells. Comparative anticancer effects of TRES and RES on pancreatic cancer suggested that TRES with higher bioavailability may be a potential agent for pancreatic cancer prevention and treatment. Further in vivo experiments and functional studies are warranted to investigate whether TRES exhibits better beneficial effects than RES in mice and humans.
机译:白藜芦醇(RES)作为抗癌剂已被广泛研究。但是,尚未充分确定具有较高生物利用度的三乙酰基白藜芦醇(TRES,RES的乙酰化类似物)的抗癌作用。我们比较评估了它们对胰腺癌细胞中细胞增殖,凋亡以及STAT3,NFκB和凋亡信号通路分子变化的影响。通过流式细胞术确定细胞凋亡。蛋白质印迹法和免疫沉淀法分别检测STAT3和NFκB的核转运和相互作用。 TRES和RES均以浓度和孵育时间依赖性的方式抑制胰腺癌细胞的生存能力,并诱导胰腺癌细胞凋亡。与RES相似,TRES抑制胰腺癌细胞中STAT3和NFκB的磷酸化,下调Mcl-1以及上调Bim和Puma。值得注意的是,我们首次观察到TRES和RES都抑制了PANC-1细胞的核转运,并中断了STAT3和NFκB的相互作用。 TRES和RES对胰腺癌的比较抗癌作用表明,具有较高生物利用度的TRES可能是预防和治疗胰腺癌的潜在药物。有必要进行进一步的体内实验和功能研究,以研究TRES在小鼠和人类中是否表现出比RES更好的有益作用。

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