右美托咪定通过HIF-1α信号通路对缺氧诱导的结直肠癌细胞增殖和侵袭的影响

Effects of Dexmedetomidine on Hypoxia-induced Proliferation and Invasion of Colorectal Cancer Cells Through HIF-1αSignaling Pathway

目的探讨右美托咪定对缺氧诱导的结直肠癌细胞增殖和侵袭的影响以及对缺氧诱导因子-1α(HIF-1α)信号通路的调节作用。方法Caco2细胞分为常氧组和缺氧组,CCK8检测细胞在12 h、24 h和48 h的增殖活性,Transwell实验检测侵袭细胞数,qRT-PCR法检测HIF-1α和VEGF mRNA表达水平,蛋白印迹法检测HIF-1α和VEGF蛋白表达水平;Caco2细胞在缺氧条件下,含不同浓度(0,5,10,20,40μmoL)右美托咪定的培养基进行培养,CCK8法检测细胞增殖活性,Transwell实验检测侵袭细胞数,qRT-PCR法检测HIF-1α和VEGF mRNA表达水平,蛋白印迹法检测HIF-1α和VEGF蛋白表达水平。结果缺氧组细胞在不同时间点的增殖活性均高于常氧组(P<0.05);缺氧组侵袭细胞数多于常氧组(P<0.05);缺氧组HIF-1α和VEGF mRNA及蛋白表达水平均高于常氧组(P<0.05);缺氧条件下,细胞增殖活性、侵袭细胞数以及HIF-1α和VEGF mRNA及蛋白表达水平均随右美托咪定浓度的升高逐渐降低(P<0.05)。结论右美托咪定可抑制缺氧条件下结肠癌细胞增殖和侵袭,其可能是通过抑制HIF-1α表达发挥作用。

Objective To investigate the effects of dexmedetomidine on hypoxic-induced proliferation and invasion of colon cancer cells and the regulation of hypoxic-induced-factor-1α(HIF-1α)signaling pathway.Methods Caco2 cells were divided into normal oxygen group and hypoxia group.The proliferative activity of cacO2 cells at 12 h,24 h and 48 h was detected by CCK8;the number of invasive cells was detected by Transwell assay;HIF-1αand VEGF mRNA expression level was detected by qRT-PCR;HIF-1αand VEGF protein expression level was detected by western blotting.Caco2 cells were cultured in medium with different concentrations(0,5,10,20,40μmoL)of dexmetropil under hypoxia conditions.Cell proliferation activity was detected by CCK8 method,the number of invasive cells was detected by Transwell assay,and HIF-1αand VEGF mRNA expression level was detected by qRT-PCR.HIF-1αand VEGF protein expression was detected by western blot.Results The proliferative activity of cells in hypoxia group was higher than that in normal oxygen group at different time points(P<0.05).The number of invasive cells in hypoxia group was higher than that in normal oxygen group(P<0.05).The mRNA and protein expression levels of HIF-1αand VEGF in hypoxia group were higher than those in normal oxygen group(P<0.05).The proliferative activity,the number of invasive cells,and the mRNA and protein expression levels of HIF-1αand VEGF were decreased with the increase of dexmedetomidine concentration(P<0.05).Conclusion Dexmetropil can inhibit the proliferation and invasion of colon cancer cells under hypoxia condition,possibly by inhibiting the expression of HIF-1α.