淫羊藿苷调控髓源抑制细胞功能抑制大肠癌转移的研究  

Study of icariin’s inhibitory effects on colorectal cancer metastasis via regulations on myeloid suppressor cells function

作　　者：栾玉玲 陈皖晴 冯煜[1] LUAN Yu-ling;CHEN Wan-qing;FENG Yu(General Surgery Department,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Academy of Integrative Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院普外科,上海200120 [2]上海中医药大学中西医结合研究院,上海200120

出　　处：《中成药》2023年第3期768-774,共7页Chinese Traditional Patent Medicine

基　　金：上海市科学技术委员会扬帆计划项目(21YF1444500)。

摘　　要：目的探讨淫羊藿苷调控髓源抑制细胞(MDSCs)功能抑制大肠癌转移的机制。方法采用不同浓度淫羊藿苷干预MDSCs细胞,CCK8法检测细胞增殖情况,流式细胞术检测MDSCs细胞凋亡、表达及分化情况,RT-qPCR法检测MDSCs细胞免疫抑制活性相关基因Arg-1、iNOS及其分化相关基因IRF8、RORC1 mRNA表达。建立MDSCs和MC38肠癌细胞共培养体系,Transwell侵袭实验检测肠癌细胞侵袭能力。结果淫羊藿苷对MDSCs细胞增殖有抑制作用,可促进MDSCs细胞凋亡(P<0.01),降低PMN-MDSCs、Mo-MDSCs表达(P<0.01),下调MDSCs细胞免疫抑制相关基因Arg-1、iNOS及分化负调控基因RORC1 mRNA表达(P<0.05,P<0.01),促进DCs表达(P<0.01),上调分化基因IRF8 mRNA表达(P<0.05,P<0.01)。此外,与对照组比较,MDSCs细胞上清能促进大肠癌细胞侵袭(P<0.01);与MDSCs组比较,淫羊藿苷干预能抑制MDSCs对肠癌细胞侵袭能力的促进作用(P<0.01)。结论淫羊藿苷可通过调控MDSCs细胞凋亡及分化抑制其免疫抑制活性,抑制大肠癌转移。AIM To explore the mechanism of regulatory effects of icariin in the metastasis of colorectal cancer and the function of myeloid suppressor cells(MDSCs).METHODS The MDSCs cells intervened with different concentrations of icariin had their cell proliferation detected by CCK8 method;their apoptosis,expression and differentiation detected by flow cytometry;and their immunosuppressive activity related mRNA expressions of genes Arg-1 and iNOS,and differentiation-related genes IRF8 and RORC1 detected by RT-qPCR.In the established coculture system of MDSCs and MC38 intestinal cancer cells,the invasiveness of the intestinal cancer cells was investigated by Transwell invasion assay.RESULTS Upon MDSCs,icariin inhibited the proliferation(P<0.01);promoted the apoptosis(P<0.01);reduced the expressions of PMN-MDSCs and Mo-MDSCs(P<0.01);down-regulated the mRNA expressions of Arg-1,iNOS and IRF8,and RORC1 as well(P<0.05,P<0.01);enhanced the DCs expression(P<0.01);and upregulated the differentiation gene IRF8 mRNA expression(P<0.05,P<0.01).In addition,compared with the untreated control group,the group treated with the MDSCs cells supernatant demonstrated promoted invasion of colorectal cancer cells(P<0.01).Compared with the MDSCs supernatant group,the group intervened with icariin could inhibit the promoting effect of MDSCs on the invasiveness ability of colorectal cancer cells(P<0.01).CONCLUSION Icariin can inhibit the metastasis of colorectal cancer by inhibiting the immunosuppressive activity of MDSCs cells via regulations on their apoptosis and differentiation.

关 键 词：淫羊藿苷 髓源抑制细胞 大肠癌转移 凋亡 免疫抑制 

分 类 号：R285.5[医药卫生—中药学]