本文選題：膀胱癌　切入點(diǎn)：順鉑　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:研究順鉑(cisplatin,DDP)能否激活人膀胱癌T24細(xì)胞自噬以及其中可能的機(jī)制,并且探索自噬和凋亡之間相關(guān)性。方法:采用Western blot技術(shù)檢測(cè)細(xì)胞內(nèi)LC3-II、P62蛋白和細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶1/2(extracellular signal-regulated kinase,ERK1/2)和磷酸化ERK1/2蛋白的表達(dá)量。檢測(cè)自噬抑制劑渥曼青霉素(wortmannin,WTM)抑制自噬后對(duì)膀胱癌T24凋亡的影響。結(jié)果:順鉑可顯著抑制T24細(xì)胞的增殖(P0.05),并呈濃度依賴性,半數(shù)抑制濃度(IC50)為(30.3±2.4)μg/mL。DDP誘導(dǎo)膀胱癌T24細(xì)胞自噬活化,使LC3-II蛋白的表達(dá)明顯升高(P0.05),P62蛋白的表達(dá)明顯下降(P0.05);細(xì)胞自噬體數(shù)目明顯增加。DDP能上調(diào)ERK1/2的磷酸化(P0.05);ERK1/2通路抑制劑U0126抑制DDP誘導(dǎo)的膀胱癌T24細(xì)胞自噬活化,使LC3-II蛋白的表達(dá)明顯下降(P0.05)。自噬抑制劑渥曼青霉素(wortmannin,WTM)抑制自噬后明顯加強(qiáng)DDP對(duì)T24細(xì)胞的增殖抑制和凋亡促進(jìn)作用(P0.05);在DDP和WTM聯(lián)合處理組,凋亡指標(biāo)多聚ADP-核糖聚合酶1(PARP 1)裂解明顯增強(qiáng),cleaved-Caspase3明顯增多(P0.05)。結(jié)論:抑制自噬活化可以增強(qiáng)膀胱癌T24細(xì)胞凋亡,證明順鉑誘導(dǎo)的自噬對(duì)膀胱癌T24細(xì)胞是保護(hù)性的,并且進(jìn)一步發(fā)現(xiàn)了自噬活化的機(jī)制可能與ERK信號(hào)通路的激活有關(guān)。
[Abstract]:Aim: to investigate whether cisplatin DDP) can activate autophagy of human bladder cancer cell line T24 and its possible mechanism. And to explore the correlation between autophagy and apoptosis. Methods: the expression of LC3-IIP62 protein and extracellular signal-regulated kinaseERK1 / 2) and phosphorylated ERK1/2 protein were detected by Western blot technique. The expression of intracellular LC3-IIP62 protein and extracellular signal-regulated kinase1 / 2 protein and phosphorylated ERK1/2 protein were detected by Western blot technique. Results: cisplatin significantly inhibited the proliferation of T24 cells in a concentration-dependent manner. IC50 was 30.3 鹵2.4 渭 g / mL DDP induced autophagy in T24 cells of bladder cancer. The expression of LC3-II protein increased significantly and the expression of P0.05 / P62 protein decreased significantly. The number of autophagy increased significantly. DDP upregulated the phosphorylation of ERK1/2 phosphorylated P0.05ERK1 / 2 pathway inhibitor U0126 inhibited DDP induced autophagy activation of bladder cancer T24 cells. The expression of LC3-II protein was significantly decreased (P 0.05). The inhibition of autophagy inhibitor, Warmensin / wortmanninnine (WTM), significantly enhanced the proliferation inhibition and apoptosis promotion of DDP on T24 cells. Apoptosis index polyADP- ribosomal polymerase 1 (PARP1) cleavage increased significantly (P 0.05). Conclusion: inhibition of autophagy activation can enhance apoptosis of T24 cells, which proves that cisplatin induced autophagy is protective to bladder cancer T24 cells. Furthermore, the mechanism of autophagy activation may be related to the activation of ERK signaling pathway.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.14

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