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
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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。Abstract: 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 IFN-γ expression 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.
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Key words:
- cordycepin /
- CD4+T lymphocytes /
- immune checkpoint inhibitors /
- PD-1 /
- PI3K/AKT
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