發(fā)布時(shí)間：2018-06-06 17:42

  本文選題：肺腺癌細(xì)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(xì)胞株中,乳酸與PD-L1表達(dá)的相關(guān)性及其可能的調(diào)控機(jī)制。方法:選取人肺腺癌細(xì)胞株A549、H1299以及Jurkat T細(xì)胞作為研究對(duì)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(dá)的相關(guān)性。(2)通過(guò)用Western blot和ELISA結(jié)合的方法,探討cAMP/PKA信號(hào)轉(zhuǎn)導(dǎo)通路與乳酸/GPR81調(diào)控PD-L1表達(dá)的相關(guān)性。(3)運(yùn)用轉(zhuǎn)染質(zhì)粒以及siRNA的方法,探討Hippo信號(hào)轉(zhuǎn)導(dǎo)通路介導(dǎo)乳酸調(diào)控PD-L1表達(dá)的機(jī)制。(4)運(yùn)用ELISA技術(shù)以及流式細(xì)胞儀檢測(cè)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(jī)制。結(jié)果:1.在肺腺癌細(xì)胞株中,乳酸促進(jìn)PD-L1表達(dá)。2.乳酸通過(guò)抑制cAMP/PKA來(lái)調(diào)控PD-L1的表達(dá)。3.Hippo/TAZ介導(dǎo)乳酸對(duì)PD-L1的調(diào)控。4.RhoA和LATS1介導(dǎo)乳酸/GPR81對(duì)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(dá)。6.乳酸誘導(dǎo)的PD-L1高表達(dá)能夠抑制免疫反應(yīng)。結(jié)論:1.乳酸/GPR81,通過(guò)Hippo-TAZ信號(hào)轉(zhuǎn)導(dǎo)通路的介導(dǎo),調(diào)控PD-L1的表達(dá)。2.乳酸可能是通過(guò)影響PD-1/PD-L1通路,抑制腫瘤微環(huán)境中T細(xì)胞的功能,達(dá)到促進(jìn)腫瘤細(xì)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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

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本文編號(hào)：1987574