本文選題：依維莫司(Everolimus + RAD001)　； 參考：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：在體外研究mTOR抑制劑依維莫司(Everolimus，RAD001)對(duì)人前列腺癌PC-3細(xì)胞增殖的改變，并探討其可能的作用機(jī)制。 方法：體外采用細(xì)胞培養(yǎng)技術(shù)培養(yǎng)人前列腺癌PC-3細(xì)胞株，使用MTT法檢測(cè)mTOR抑制劑依維莫司(Everolimus，RAD001)1nmol/l干預(yù)人前列腺癌PC-3細(xì)胞株24h、36h、48h、72h后，PC-3細(xì)胞株增殖的變化；流式細(xì)胞分析技術(shù)（FCM）檢測(cè)mTOR抑制劑依維莫司(Everolimus，RAD001)干預(yù)人前列腺癌PC-3細(xì)胞株24h、36h、48h、72h后，細(xì)胞周期的變化；Western blot檢測(cè)mTOR抑制劑依維莫司(Everolimus，RAD001)干預(yù)人前列腺癌PC-3細(xì)胞株24h、36h、48h、72h后，p-4E-BP1和p-P70-S6K的表達(dá)情況。采用SPSS13.0統(tǒng)計(jì)軟件對(duì)實(shí)驗(yàn)所得數(shù)據(jù)分析， P＜0.05有統(tǒng)計(jì)學(xué)差異。 結(jié)果： 1MTT結(jié)果顯示，mTOR抑制劑依維莫司(Everolimus，RAD001)可抑制人前列腺癌PC-3細(xì)胞株的增值，且隨著藥物干預(yù)時(shí)間的延長(zhǎng)，，抑制率逐步增大（P0.01）。 2流式細(xì)胞分析技術(shù)（FCM）結(jié)果顯示，人前列腺癌PC-3細(xì)胞株經(jīng)mTOR抑制劑依維莫司(Everolimus，RAD001)干預(yù)后，隨著藥物干預(yù)時(shí)間的延長(zhǎng)，G0/G1期的細(xì)胞百分比逐步升高，S、G2/M期的細(xì)胞百分比逐步降低，使絕大部分PC-3細(xì)胞被中斷在細(xì)胞周期的G0/G1期（P＜0.01）。 3Western blot檢測(cè)結(jié)果顯示，mTOR抑制劑依維莫司(Everolimus，RAD001)干預(yù)人前列腺癌PC-3細(xì)胞株后，隨著藥物干預(yù)時(shí)間的延長(zhǎng)，p-4E-BP1和p-P70-S6K的表達(dá)逐步被抑制（P0.01）。 結(jié)論： mTOR抑制劑依維莫司(Everolimus，RAD001)能夠抑制人前列腺癌PC-3細(xì)胞株的增值，其機(jī)制可能與PI3K/Akt/mTOR信號(hào)傳導(dǎo)通路中的mTOR被抑制，繼而抑制了其下游的兩個(gè)重要蛋白（即翻譯抑制因子eIF-4E結(jié)合蛋白1(4E-BP1)和核糖體蛋白P70-S6K）的磷酸化有關(guān)。
[Abstract]:Aim: to investigate the effect of Everolimus RAD001, an inhibitor of mTOR, on the proliferation of human prostate cancer cell line PC-3 in vitro and to explore its possible mechanism. Methods: human prostate cancer PC-3 cell line was cultured by cell culture technique in vitro. The proliferation of human prostate cancer PC-3 cell line was measured by MTT assay after treatment with 1nmol/l for 24 h, 36 h and 48 h, respectively. Flow cytometry (FCM) was used to detect the expression of p-4E-BP1 and p-P70-S6K in human prostate cancer PC-3 cells treated with Everolimus RAD001, a mTOR inhibitor, for 24 h or 36 h or 48 h or 72 h. The changes of cell cycle were detected by Western blot. The expression of p-4E-BP1 and p-P70-S6K in human prostate cancer cell line PC-3 treated with Everolimusine RAD001 for 24 h, 36 h, 48 h and 72 h later. SPSS 13.0 statistical software was used to analyze the experimental data (P < 0.05). Results: 1MTT results showed that Everolimus RAD001, an inhibitor of mTOR, inhibited the proliferation of human prostate cancer cell line PC-3. The inhibition rate increased gradually (P0.01). 2 the results of flow cytometry (FCM) showed that human prostate cancer PC-3 cell line was treated with the mTOR inhibitor Everolimus ARAD001. The percentage of cells in G _ 0 / G _ 1 phase increased gradually with the prolongation of drug intervention time, and the percentage of cells in G _ 2 / M phase decreased gradually. The majority of PC-3 cells were interrupted in G0 / G1 phase of cell cycle (P < 0. 01). 3 the results of Western blot analysis showed that human prostate cancer PC-3 cell line was treated with Everolimus Rad001, an inhibitor of mTOR. The expression of p-4E-BP1 and p-P70-S6K was inhibited gradually with the prolongation of drug intervention time (P0.01). Conclusion: Everolimus RAD001, an inhibitor of mTOR, can inhibit the proliferation of human prostate cancer cell line PC-3, and its mechanism may be related to the inhibition of mTOR in the PI3K / Akt / mTOR signaling pathway. The phosphorylation of two important proteins downstream, the translation inhibitory factor eIF-4E binding protein 1 (4E-BP1) and ribosomal protein P70-S6K, was subsequently inhibited.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25

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本文編號(hào)：2068996