姜黄素对宫颈癌细胞系中c-Jun及JAK-STAT信号传导通路的影响机制研究

Effect of curcumin on c-Jun and JAK-STAT signaling pathways in cervical cancer cell lines

目的:探讨姜黄素对宫颈癌细胞系中c-Jun及JAK-STAT信号传导通路的影响机制。方法:将宫颈癌Hela细胞分为不同浓度(5μmol/L、10μmol/L、25μmol/L、50μmol/L)实验组和对照组,实验组用不同浓度的姜黄素进行处理,对照组不予处理。采用MTT法检测各组Hela细胞增殖抑制率,Western blot法检测细胞JAK1、JAK2、STAT3、c-Fos及c-Jun蛋白表达水平,实时荧光定量聚合酶链反应(q PCR)法检测细胞JAK1、JAK2、STAT3 mRNA相对表达量。结果:与对照组比较,姜黄素作用24 h、48 h、72 h后,10μmol/L组、25μmol/L组、50μmol/L组细胞增殖抑制率明显升高(P<0.05)。与对照组比较,10μmol/L组、25μmol/L组、50μmol/L组细胞c-Fos、c-Jun蛋白表达水平及JAK1、JAK2、STAT3 mRNA和蛋白表达水平均明显降低(均P<0.05),且药物浓度越高,对相关基因和蛋白表达的抑制作用越明显。结论:姜黄素能够地抑制宫颈癌Hela细胞增殖,且存在剂量和时间依赖性,其作用机制可能与下调c-Fos及c-Jun蛋白表达,降低细胞内JAK-STAT信号传导通路活性有关。

Objective:To investigate the effect of curcumin on c-Jun and JAK-STAT signaling pathways in cervical cancer cell lines.Methods:Cervical cancer Hela cells were divided into control group and experimental groups with different concentrations of curcumin(5μmol/L,10μmol/L,25μmol/L,50μmol/L).The experimental groups were treated with curcumin at different concentrations,while the control group received no curcumin.MTT assay was employed to detect the proliferation inhibition rate of Hela cells in each group,Western blot was used to detect the expression levels of JAK1,JAK2,STAT3,c-Fos and c-Jun proteins,and qRT-PCR was used to detect the relative mRNA expression of JAK1,JAK2,and STAT3.Results:Compared with the control group,the inhibition rate of cell proliferation in the 10μmol/L group,25μmol/L group,and 50μmol/L group was significantly increased after curcumin treatment for 24 h,48 h,and 72 h(P<0.05).Compared with the control group,the expression levels of c-Fos,c-Jun protein,the mRNA expression levels of JAK1,JAK2,STAT3 and protein in 10μmol/L group,25μmol/L group,and 50μmol/L group were significantly reduced(all P<0.05),and the higher the drug concentration,the more inhibitory effect on the expression of related genes and proteins.Conclusion:Curcumin can inhibit the proliferation of cervical cancer Hela cells in a doseand time-dependent manner,and its mechanism may be related to down-regulating the expression of c-Fos and c-Jun proteins and reducing the activity of intracellular JAK-STAT signaling pathways.