臭牡丹总黄酮通过Keap1/Nrf2/ARE信号通路对胃癌SGC7901细胞增殖、迁移和侵袭的影响

目的:探讨臭牡丹总黄酮(total flavone of clerodendrum bungei，TFCB)通过Keap1/Nrf2/ARE信号通路对胃癌SGC7901细胞增殖、迁移和侵袭的影响。方法:用臭牡丹总黄酮溶液干预人胃癌SGC7901细胞，然后采用MTT法检测TFCB对SGC7901细胞增殖能力的影响；划痕修复及Transwell小室侵袭实验检测TFCB对SGC7901细胞迁移和侵袭能力的影响；Western blot及RT-PCR法检测TFCB对SGC7901细胞Keap1、Nrf2及maf蛋白及mRNA表达的影响。结果:低、中、高剂量组TFCB均显著抑制了SW620细胞的增殖、迁移和侵袭，随着药物干预浓度的增加，抑制程度逐渐增加。与空白对照组比较，低剂量干预组TFCB处理后Nrf2及maf蛋白相对表达量均显著下降(P＜0.05)，Keap1蛋白相对表达量显著升高(P＜0.05)，但Keap1、Nrf2及maf mRNA表达量无显著的统计学差异(P＞0.05)；高中剂量干预组TFCB处理后Nrf2及maf蛋白及mRNA相对表达量亦显著下降，Keap1蛋白及mRNA表达量显著升高，并且在高中低剂量干预组间Keap1、Nrf2及maf蛋白及mRNA相对表达量均有统计学差异(P＜0.05)。结论:TFCB可明显抑制人胃癌SGC7901细胞的增殖、迁移和侵袭，且其作用机制可能与TFCB阻滞Keap1-Nrf2-ARE信号通路的信号传导，抑制通路蛋白及mRNA合成有关。

Effects of total flavone of clerodendrum bungei on proliferation,migration and invasion of gastric cancer SGC7901 cells by Keap1/Nrf2/ARE signaling pathway

Objective:To investigate the effects of total flavone of clerodendrum bungei (TFCB) on the proliferation,migration and invasion of gastric cancer SGC7901 cells by Keap1/Nrf2/ARE signaling pathway.Methods:Human gastric cancer SGC7901 cells were treated with TFCB solution,and then the effect of TFCB on the proliferation of SGC7901 cells was detected by MTT assay.Scratch repair and Transwell chamber invasion assay were used to detect the effect of migration and invasion ability on SGC7901 cells.Western blot and RT-PCR method detected the effect of TFCB on the expression of Keap1,Nrf2 and maf protein and mRNA in SGC7901 cells.Results:The low,middle and high dose groups of TFCB significantly inhibited the proliferation,migration and invasion of SW620 cells (P＜0.05).With the increase of drug intervention concentration,the degree of inhibition increased gradually.Compared with the control group,the relative expression of Nrf2 and maf protein in the low-dose group of TFCB decreased significantly,and the protein expression of Keap1 was significantly increased (P＜0.05),but there was no statistically significant difference in the mRNA expression of Keap1,Nrf2 and maf (P＞0.05).The relative expression levels of Nrf2 and maf protein and mRNA were also significantly decreased in high and middle dose groups of TFCB,and Keap1 protein and mRNA expression was significantly increased (P＜0.05).The relative expression levels of Keap1,Nrf2 and maf protein and mRNA in the high,middle and low dose groups of TFCB were significantly different (P＜0.05).Conclusion:TFCB can significantly inhibit the proliferation,migration and invasion of human gastric cancer SGC7901 cells,and its mechanism may be related to the signal transduction of Keap1-Nrf2-ARE signaling pathway and the inhibition of pathway protein and mRNA synthesis by TFCB.