Objective To investigate the effect of ginseng-derived compound K (C-K) on apoptosis, immunosuppressive activity, and pro-inflammatory cytokine production of myeloid-derived suppressor cells (MDSCs) from mice bearing colorectal cancer xenograft. Methods Flow-sorted bone marrow MDSCs from Balb/c mice bearing CT26 tumor xenograft were treated with either C-K or PBS for 96 h and examined for apoptosis with Annexin V/7-AAD, Cox-2 and Arg-1 expressions using qRT-PCR, and supernatant IL-1β, IL-6, and IL-17 levels with ELISA. C-K-or PBS-treated MDSCs were subcutaneously implanted along with CT26 tumor cells in WT Balb/c mice, and the tumor size and morphology were evaluated 21 days later. Results C-K treatment significantly increased the percentages of early and late apoptotic MDSCs in vitro (P<0.01 and P<0.05, respectively), decreased the expressions of immunosuppression-related genes Cox-2 (P<0.05) and Arg-1 (P<0.01), and suppressed the production of IL-1β (P<0.05), IL-6 (P<0.01), and IL-17 (P<0.05) by the MDSCs . Compared with PBS-pre-treated cells, C-K-pretreated MDSCs showed significantly attenuated activity in promoting CT26 tumor growth in mice (P<0.01). Conclusion C-K can suppress the immunosuppresive effect of MDSCs to inhibit tumor cell proliferation in mice, which suggests a new strategy of tumor therapy by targeting MDSCs.%目的:探讨人参皂苷Compound K(C-K)对髓系抑制性细胞(myeloid derived suppressor cell, MDSC)凋亡、免疫抑制及促炎症细胞因子分泌的影响。方法流式细胞术分选得到CT26肿瘤小鼠骨髓MDSCs,分别用C-K或PBS处理后,Annexin V/7-AAD检测细胞凋亡;qRT-PCR检测Cox-2和Arg-1的mRNA表达水平;ELISA技术检测细胞培养上清中IL-1β、IL-6和IL-17的水平。体内实验中,C-K或对照PBS处理的MDSCs和结肠癌细胞系CT26共同皮下免疫Balb/c小鼠,21 d后,对两组小鼠肿瘤的大小以及组织形态学进行鉴定。结果 C-K促进了体外培养的MDSC的凋亡,表现为早期细胞凋亡率及晚期凋亡细胞或坏死率均增加(P<0.01,P<0.05);并显著下调了MDSC中免疫抑制作用相关基因Cox-2及Arg-1的表达(P<0.05,P<0.01);同时抑制了MDSC中促炎症细胞因子IL-1β、IL-6和IL-17的分泌(P<0.05,P<0.001,P<0.05)。与对照组比较,C-K处理后的MDSCs在体内促进肿瘤细胞的增殖作用明显减弱(P<0.01)。结论 C-K能促进体外培养的MDSC细胞凋亡并拮抗其免疫抑制功能,从而抑制肿瘤细胞的生长与增殖。
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