丙泊酚调控HIF-1α表达靶向SIRT1信号通路对胰腺癌细胞增殖凋亡的影响

Effect of propofol on proliferation and apoptosis of pancreatic cancer cells by regulating HIF-1αexpression and targeting SIRT1 signaling pathway

目的探讨丙泊酚对胰腺癌细胞增殖凋亡的影响,进一步分析丙泊酚对胰腺癌细胞中缺氧诱导因子-1α(HIF-1α)和沉默信号调节因子1(SIRT1)信号通路的影响。方法分别采用5μg/ml和10μg/ml的丙泊酚处理胰腺癌Panc-1细胞48 h,设置control组、低剂量组和高剂量组。采用CCK8检测各组细胞的增殖能力,采用Hoechst 33258对各组细胞的凋亡指标进行检测,应用ELISA法测定各组细胞的炎症因子水平,应用qPCR法对SIRT1信号通路mRNA的表达水平进行评判。结果与control组相比,低剂量组、高剂量组的增殖能力显著降低(P<0.01),凋亡水平显著升高(P<0.01);炎症因子IL-6(P<0.01)和IL-1β(P<0.01)水平显著升高,凋亡相关蛋白Fas和FasL的表达显著升高(P<0.01),Bcl-2/Bax显著降低(P<0.01),HIF-1αmRNA的表达水平显著升高(P<0.01),SIRT1 mRNA的表达水平显著降低(P<0.01),HIF-1α蛋白的表达水平均显著升高(P<0.01),SIRT1蛋白的表达水平显著降低(P<0.01)。结论丙泊酚调控HIF-1α表达靶向SIRT1信号通路会促进胰腺癌细胞增殖,加速凋亡。

Objective To investigate the effect of propofol on proliferation and apoptosis of pancreatic cancer cells,and to further analyze the effect of propofol on hypoxia-inducible factor-1α(HIF-1α)and silencing signal regulator 1(SIRT1)signaling pathway in pancreatic cancer cells.Methods Pancreatic cancer Panc-1 cells were treated with 5μg/ml and 10μg/ml propofol for 48 h,respectively.The control group,low-dose group,and high-dose group were set.CCK8 was used to detect the proliferation ability of cells in each group.Hoechst 33258 was used to detect the details of apoptotic indicators of cells in each group.ELISA was used to determine the levels of inflammatory factors in each group,and qPCR was used to evaluate the expression levels of SIRT1 signaling pathway mRNA.Results Compared with the control group,the proliferation ability of the low-dose group and the high-dose group was significantly reduced(P<0.01);the apoptosis level was significantly increased(P<0.01);the inflammatory factor IL-6(P<0.01)and IL-1β(P<0.01)increased significantly;the expression of apoptosis-related proteins Fas and FasL was significantly increased(P<0.01);Bcl-2/Bax was significantly decreased(P<0.01);the expression level of HIF-1αmRNA was significantly increased(P<0.01);the expression level of SIRT1 mRNA was significantly decreased(P<0.01);the expression levels of HIF-1αprotein were significantly increased(P<0.01);and the expression level of SIRT1 protein was significantly decreased(P<0.01).Conclusion Propofol regulating HIF-1αexpression targeting the SIRT1 signaling pathway can promote the proliferation of pancreatic cancer cells and accelerate apoptosis.