白藜芦醇通过诱导G MDSCs凋亡和M MDSCs分化延缓Lewis荷瘤小鼠肿瘤生长

目的: 探讨白藜芦醇对髓源抑制性细胞(myeloid derived suppressor cells， MDSCs)的影响及其抗肿瘤免疫的作用。方法: 建立小鼠Lewis肺癌移植瘤模型，用白藜芦醇(白藜芦醇组，n=6)和PBS(对照组，n=6)分别灌胃处理，测量肿瘤体积和重量；用流式细胞术检测小鼠体内各群MDSCs细胞比率；用免疫磁珠分选技术分离出荷瘤小鼠脾脏粒系MDSCs(G MDSCs)及单核系MDSCs(M MDSCs)，经白藜芦醇分别刺激12 h后，流式细胞术检测G MDSCs凋亡及M MDSCs分化情况。结果： 与对照组比较，白藜芦醇组荷瘤小鼠肿瘤体积显著减小(P<0.05)，肿瘤重量减轻(P<0.01)，脾脏中总MDSCs、M MDSCs比率无明显变化，G MDSCs比率下调；肿瘤组织中总MDSCs和G MDSCs比率均显著减少（P均<0.05），M MDSCs比率无显著差异。白藜芦醇分别处理G MDSCs、M MDSCs后，早期和晚期凋亡的G MDSCs总数明显高于对照组，M MDSCs表面CD11c和F4/80的表达显著上调。 结论： 白藜芦醇可通过促进G MDSCs凋亡和M MDSCs分化抑制肿瘤生长。

Resveratrol delays tumor progression in Lewis lung cancer bearing mice by inducing apoptosis of G-MDSCs

Objective: To investigate the influence of resveratrol on myeloid derived suppressor cells (MDSCs) and its role in anti tumor immunity. Methods: The Lewis lung carcinoma tumor bearing mice models were established and orally treated with resveratrol(resveratrol group, n=6) and PBS(control group, n=6) respectively, the volumes and weights of tumors were measured; the proportions of different subsets of MDSCs infiltrated in spleens and tumor tissues of tumor bearing mice were examined by flow cytometry(FCM). G MDSCs and M MDSCs were isolated from splenocytes of tumor bearing mice by magnetic activated cell sorting (MACS). After stimulated with resveratrol for 12 h, FCM was used to examine the apoptosis of G MDSCs and the differentiation of M MDSCs. Results: Compared with the control group, the tumor volumes and weights of tumor bearing mice in resveratrol group were significantly decreased(P<0.01,P<0.05); the results of FCM indicated that the percentages of total MDSCs and M MDSCs in spleens of tumor bearing mice showed no significant difference, while the percentages of G MDSCs were reduced; and in tumor tissues, the frequencies of both total MDSCs and G MDSCs were decreased, but the frequencies of M MDSCs showed no marked difference. The isolated G MDSCs and M MDSCs were separately treated with resveratrol for 12h, the early and late apoptotic G MDSCs were higher than those in control group and the expression levels of CD11c and F4/80 on M MDSCs were both significantly upregulated. Conclusion: Resveratrol may inhibit tumor growth by promoting the apoptosis of G MDSCs and the differentiation of M-MDSCs.