人参皂苷Rg3激活MAPK/ERK信号通路促进T细胞功能的抗肿瘤机制

The antitumor mechanism of ginsenoside Rg3 activating MAPK/ERK pathway to promote T cell function

目的探讨人参皂苷Rg3调节CD8^(+)T细胞功能从而增加抗肿瘤的作用,并阐明其作用机制。方法MTT法检测Rg3对CD8^(+)T细胞的影响以及对Rg3作用后的CD8^(+)T细胞对黑色素瘤B16F10的杀伤能力,并通过显微镜进行细胞形态学观察;EDU检测B16F10细胞增殖情况;流式细胞术分析对CD8^(+)T细胞功能作用;Western blot检测相关蛋白表达;实时定量PCR检测mRNA变化。结果Rg3可显著增加CD8^(+)T细胞对肿瘤细胞的杀伤能力,并促进功能性记忆T细胞的转化。Rg3增加T细胞释放杀伤因子IL-2及IFN-γ及其mRNA的表达,增加功能性T细胞(central memory T cell,TCM)的比例。进一步数据显示,Rg3促进功能性T细胞分化进而促进T细胞杀伤活性抗肿瘤与激活MAPK/ERK通路正相关。结论人参皂苷Rg3通过激活MAPK/ERK通路促进CD8^(+)T淋巴细胞的杀伤性作用而增加抗肿瘤作用。

Aim To elucidate the mechanism by which Rg3 regulates the function of CD8^(+)T cells to increase the anti-tumor effect.Methods MTT assay was used to detect the effect of Rg3 on CD8^(+)T cells and the killing ability of CD8^(+)T cells against melanoma B16F10,and microscopy was used to observe cell morphology.EDU was applied to detect the proliferation of B16F10 cells.Flow cytometry was used to analyze the function of CD8^(+)T cells.Western blot was used to detect the expression of related proteins.Real-time quantitative PCR was employed to detect the changes of mRNA.Results Rg3 could significantly increase the killing ability of CD8^(+)T cells to tumor cells and promote the transformation of functional memory T cells.Rg3 elevated killer factors IL-2,IFN-γ secretion and expression of mRNA,and increased the proportion of central memory T cell(TCM).Further data showed that Rg3 promoted functional T cell differentiation and then promoted killing activity and anti-tumor activity of T cell,which was positively correlated with the activation of MAPK/ERK pathway.Conclusions Ginsenoside Rg3 enhances the anti-tumor effect of CD8^(+)T lymphocytes by activating MAPK/ERK pathway.