本文選題：肺腺癌細胞株 + 乳酸�。� 參考：《皖南醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:本課題旨在探討肺腺癌細胞株中,乳酸與PD-L1表達的相關(guān)性及其可能的調(diào)控機制。方法:選取人肺腺癌細胞株A549、H1299以及Jurkat T細胞作為研究對象。(1)用Western blot和QPCR相結(jié)合的方法,探討乳酸與TAZ和PD-L1表達的相關(guān)性。(2)通過用Western blot和ELISA結(jié)合的方法,探討cAMP/PKA信號轉(zhuǎn)導(dǎo)通路與乳酸/GPR81調(diào)控PD-L1表達的相關(guān)性。(3)運用轉(zhuǎn)染質(zhì)粒以及siRNA的方法,探討Hippo信號轉(zhuǎn)導(dǎo)通路介導(dǎo)乳酸調(diào)控PD-L1表達的機制。(4)運用ELISA技術(shù)以及流式細胞儀檢測凋亡的技術(shù),分析腫瘤微環(huán)境的代謝產(chǎn)物乳酸與免疫逃逸的相關(guān)性,以及可能的機制。結(jié)果:1.在肺腺癌細胞株中,乳酸促進PD-L1表達。2.乳酸通過抑制cAMP/PKA來調(diào)控PD-L1的表達。3.Hippo/TAZ介導(dǎo)乳酸對PD-L1的調(diào)控。4.RhoA和LATS1介導(dǎo)乳酸/GPR81對PD-L1的調(diào)控。5.TAZ-TEAD1復(fù)合體介導(dǎo)乳酸誘導(dǎo)的PD-L1表達。6.乳酸誘導(dǎo)的PD-L1高表達能夠抑制免疫反應(yīng)。結(jié)論:1.乳酸/GPR81,通過Hippo-TAZ信號轉(zhuǎn)導(dǎo)通路的介導(dǎo),調(diào)控PD-L1的表達。2.乳酸可能是通過影響PD-1/PD-L1通路,抑制腫瘤微環(huán)境中T細胞的功能,達到促進腫瘤細胞免疫逃逸。
[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.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2

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本文編號：1987574