虫草素通过调节CD4^+T淋巴细胞PD-1受体促进肿瘤免疫及机制研究  

Mechanismof Cordycepin Promotes Tumor Immunity by Regulating PD-1 Receptor of CD4^+ T Lymphocytes

作　　者：安青[1] 何立巍 吴红雁 侯宪邦 张洪江 朱安宏 张晓平 范方田 AN Qing;HE Li-wei;WU Hong-yan;HOU Xian-bang;ZHANG Hong-jiang;ZHU An-hong;ZHANG Xiao-ping;FAN Fang-tian(Department of Integrated Traditional Chinese and Western Medicine,Jiangsu Cancer Hospital,Nanjing,210009,China;Hanlin College,Nanjing University of Chinese Medicine,Taizhou,225312,China;Research Center of Biomedical Technology,Jiangsu Vocational College of Medicine,Yancheng,224005,China)

机构地区：[1]江苏省肿瘤医院中西医结合科,江苏南京210009 [2]南京中医药大学翰林学院,江苏泰州225312 [3]江苏医药职业学院医药生物技术研究院,江苏盐城224005

出　　处：《南京中医药大学学报》2018年第5期495-498,共4页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81473316;81603463);中国博士后基金面上项目(2017M611873);江苏省博士后基金(1701120C);江苏省自然科学基金(BK20151356;BK20161320);江苏省高校自然科学基金(16KJB360008);江苏省中医药管理局科技项目(YB2017091);江苏省教育厅"青蓝工程"青年骨干教师培养项目(2016;2017)

摘　　要：目的探讨虫草素体外对肿瘤相关CD4^+T淋巴细胞肿瘤杀伤作用及其内在机制。方法通过移植瘤分离得到肿瘤相关CD4^+T淋巴细胞,运用MTS法研究虫草素对肿瘤相关CD4^+T淋巴细胞增殖作用的影响,运用LDH法研究虫草素处理后的肿瘤相关CD4^+T淋巴细胞对于其共孵育肿瘤细胞的杀伤作用,运用ELISA法对CD4^+T淋巴细胞与肿瘤细胞共孵育后的细胞上清中的细胞因子进行检测,同时运用Western blot法对虫草素处理后的CD4^+T淋巴细胞中的相关蛋白进行研究。结果虫草素能够促进肿瘤相关CD4^+T淋巴细胞的增殖和杀伤作用且呈现出一定的剂量依赖性,虫草素能够降低肿瘤相关CD4^+T淋巴细胞的PD-1蛋白表达,增强PI3K/AKT信号通路相关蛋白的表达且促进IL-2、IFN-γ的表达。结论虫草素能够促进肿瘤相关CD4^+T淋巴细胞的增殖和杀伤作用,其机制可能与抑制肿瘤免疫检查点PD-1有关。OBJECTIVE To investigate the mechanism of killing effect of cordycepin on tumor associated CD4+T lymphocyte tumor in vitro.METHODS Tumor associated CD4+T lymphocytes were isolated from xenograft tumors.MTS assay was used to study the effect of cordycepin on the proliferation of tumor associated CD4+T lymphocytes;LDH method was used to analyze the killing effect of tumor associated CD4+T lymphocytes treated with cordycepin.For the co incubation of tumor cells,the cytotoxicity of the supernatants of the cells incubated with CD4+T lymphocytes and tumor cells was detected by ELISA,and Western blot was used to study the related protein in the PI3K/AKT pathway.RESULTS Cordycepin could promote the proliferation and killing effect of tumor associated CD4+T lymphocytes in a dose dependent manner,and cordycepin reduced PD-1 protein and enhanced PI3K/AKT pathway associated protein expression and promote IL-2 and IFNγexpression in tumor associated CD4+T lymphocytes.CONCLUSION Cordycepin can promote the proliferation and killing effect of tumor associated CD4+T lymphocytes and its mechanism may be related to the inhibition of tumor immune checkpoint PD-1.

关 键 词：虫草素 CD4+T淋巴细胞 免疫检查点抑制剂 PD-1 PI3K/AKT 

分 类 号：R285.5[医药卫生—中药学]