乳酸在肺腺癌细胞株中调控PD-L1表达的研究

发布时间：2018-06-06 17:42

本文选题：肺腺癌细胞株 + 乳酸　；参考：《皖南医学院》2017年硕士论文

【摘要】：目的:本课题旨在探讨肺腺癌细胞株中,乳酸与PD-L1表达的相关性及其可能的调控机制。方法:选取人肺腺癌细胞株A549、H1299以及Jurkat T细胞作为研究对象。(1)用Western blot和QPCR相结合的方法,探讨乳酸与TAZ和PD-L1表达的相关性。(2)通过用Western blot和ELISA结合的方法,探讨cAMP/PKA信号转导通路与乳酸/GPR81调控PD-L1表达的相关性。(3)运用转染质粒以及siRNA的方法,探讨Hippo信号转导通路介导乳酸调控PD-L1表达的机制。(4)运用ELISA技术以及流式细胞仪检测凋亡的技术,分析肿瘤微环境的代谢产物乳酸与免疫逃逸的相关性,以及可能的机制。结果:1.在肺腺癌细胞株中,乳酸促进PD-L1表达。2.乳酸通过抑制cAMP/PKA来调控PD-L1的表达。3.Hippo/TAZ介导乳酸对PD-L1的调控。4.RhoA和LATS1介导乳酸/GPR81对PD-L1的调控。5.TAZ-TEAD1复合体介导乳酸诱导的PD-L1表达。6.乳酸诱导的PD-L1高表达能够抑制免疫反应。结论:1.乳酸/GPR81,通过Hippo-TAZ信号转导通路的介导,调控PD-L1的表达。2.乳酸可能是通过影响PD-1/PD-L1通路,抑制肿瘤微环境中T细胞的功能,达到促进肿瘤细胞免疫逃逸。
[Abstract]:Aim: to investigate the relationship between lactic acid and PD-L1 expression in lung adenocarcinoma cell lines and its possible regulatory mechanisms. Methods: human lung adenocarcinoma cell lines A549H1299 and Jurkat T cells were selected as study objects. Western blot and QPCR were used to study the correlation between lactic acid and the expression of TAZ and PD-L1. To investigate the correlation between cAMP / PKA signal transduction pathway and the regulation of PD-L1 expression by lactate / GPR81. To explore the mechanism of regulation of PD-L1 expression mediated by Hippo signal transduction pathway. Using Elisa and flow cytometry to detect apoptosis, to analyze the correlation between lactate and immune escape in tumor microenvironment and its possible mechanism. The result is 1: 1. In lung adenocarcinoma cells, lactic acid promotes PD-L1 expression. Lactic acid regulates PD-L1 expression by inhibiting cAMP-PKA. 3. Hippo-TAZ mediates lactic acid regulation of PD-L1. 4. RhoA and LATS1 mediated regulation of PD-L1 by lactic acid / GPR81. 5. TAZ-TEAD1 complex mediates lactic acid induced PD-L1 expression. The high expression of PD-L1 induced by lactic acid can inhibit the immune response. Conclusion 1. The expression of PD-L1 was regulated by the Hippo-TAZ signal transduction pathway mediated by lactate / GPR81. Lactic acid may inhibit the function of T cells in tumor microenvironment by affecting PD-1 / PD-L1 pathway to promote the immune escape of tumor cells.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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