本文選題：來(lái)那度胺 + 阿司匹林　； 參考：《南昌大學(xué)》2015年碩士論文

【摘要】：目的:1、觀察來(lái)那度胺(lenalidomide,LEN)和阿司匹林(aspirin,ASA)聯(lián)合對(duì)骨髓瘤細(xì)胞株增殖、凋亡與細(xì)胞周期的影響,分析兩者在骨髓瘤細(xì)胞株中的相互作用。2、檢測(cè)LEN和ASA聯(lián)合對(duì)骨髓瘤細(xì)胞VEGF蛋白及wnt/β-catenin信號(hào)通路蛋白表達(dá)的影響,探討ASA對(duì)LEN抗骨髓瘤的增敏機(jī)制。方法:1、常規(guī)培養(yǎng)骨髓瘤細(xì)胞株(MM1.S及RPMI-8226),制作細(xì)胞生長(zhǎng)曲線,選取對(duì)數(shù)生長(zhǎng)期細(xì)胞進(jìn)行后續(xù)實(shí)驗(yàn)。2、采用CCK-8法檢測(cè)LEN和ASA聯(lián)合用藥對(duì)MM1.S細(xì)胞和RPMI-8226細(xì)胞增殖的影響。3、采用Annexin V-FITC/PI染色方法檢測(cè)LEN和ASA聯(lián)合用藥對(duì)MM1.S細(xì)胞和RPMI-8226細(xì)胞凋亡的影響。4、采用流式細(xì)胞儀檢測(cè)LEN和ASA聯(lián)合用藥對(duì)MM1.S細(xì)胞和RPMI-8226細(xì)胞周期的影響。5、Western Blot法檢測(cè)LEN和ASA聯(lián)合用藥對(duì)MM1.S細(xì)胞和RPMI-8226細(xì)胞VEGF蛋白、β-catenin及下游分子cyclinD1蛋白表達(dá)的影響。結(jié)果:1、藥物作用24~72 h后,LEN與ASA聯(lián)合以時(shí)間依賴(lài)性抑制細(xì)胞增殖活性,且顯著高于LEN(1μM)及ASA(2.5 mM)單藥組。相互作用分析顯示:LEN與ASA在抗MM細(xì)胞增殖中呈協(xié)同作用。2、藥物作用48 h后,LEN與ASA聯(lián)合組對(duì)MM1.S及RPMI-8226細(xì)胞凋亡誘導(dǎo)率顯著高于LEN或ASA單藥組。3、藥物作用48 h后,與LEN或ASA單藥組相比,LEN與ASA聯(lián)合組誘導(dǎo)MM1.S及RPMI-8226細(xì)胞阻滯于G1期比率明顯增高。4、藥物作用48 h后,相比LEN或ASA單藥組,兩者聯(lián)合后顯著下調(diào)了MM1.S及RPMI-8226細(xì)胞VEGF蛋白表達(dá)。5、在MM1.S與RPMI-8226細(xì)胞中,LEN作用72 h后誘導(dǎo)胞核內(nèi)β-catenin蛋白及其下游cyclin D1蛋白表達(dá)上調(diào),而ASA促使胞漿β-catenin磷酸化,導(dǎo)致胞核內(nèi)β-catenin蛋白其下游分子cyclin D1蛋白表達(dá)下降。結(jié)論:1、阿司匹林與來(lái)那度胺在抑制骨髓瘤細(xì)胞增殖中呈協(xié)同作用;2、阿司匹林通過(guò)下調(diào)骨髓瘤細(xì)胞株VEGF表達(dá)對(duì)來(lái)那度胺發(fā)揮協(xié)同抗骨髓瘤作用;3、阿司匹林通過(guò)促進(jìn)細(xì)胞漿β-catenin磷酸化,從而阻止β-catenin入細(xì)胞核發(fā)揮對(duì)來(lái)那度胺的化療增敏作用。
[Abstract]:Objective: to observe the effects of the combination of renalidomide en and aspirin on the proliferation, apoptosis and cell cycle of myeloma cell line. To investigate the effect of LEN and ASA on the expression of VEGF protein and wnt/ 尾 -catenin signal pathway protein in myeloma cell line, and to explore the mechanism of ASA on anti-myeloma. Methods: cell growth curves were prepared by routine culture of myeloma cell lines MM1.S and RPMI-8226. Logarithmic growth phase cells were selected for follow-up experiment. CCK-8 assay was used to detect the effect of combined use of LEN and ASA on the proliferation of MM1.S cells and RPMI-8226 cells. Annexin V-FITC/PI staining was used to detect the apoptosis of MM1.S cells and RPMI-8226 cells treated with LEN and ASA. The effect of combined use of LEN and ASA on the cell cycle of MM1.S and RPMI-8226 was detected by flow cytometry. The effects of LEN and ASA on the expression of VEGF protein, 尾 -catenin and cyclinD1 in MM1.S and RPMI-8226 cells were detected by Western Blot assay. Results the cell proliferation activity was inhibited in a time-dependent manner by the combination of Len and ASA for 24 ~ 72 h, and was significantly higher than that in LEN(1 渭 M and ASA(2.5 mm) groups. The results of interaction analysis showed that ASA and WLEN had synergistic effects on the proliferation of MM cells. After 48 h of drug treatment, the apoptotic induction rate of MM1.S and RPMI-8226 cells in the combination group was significantly higher than that in the LEN or ASA group, and 48 h after the drug treatment, the apoptosis induction rate of MM1.S and RPMI-8226 cells in the combination group was significantly higher than that in the single drug LEN or ASA group. Compared with LEN or ASA monotherapy group, the ratio of MM1.S and RPMI-8226 cell arrest in G1 phase was significantly increased in ASA combined with ASA group. After 48 h of treatment, compared with LEN or ASA group, the ratio of MM1.S and RPMI-8226 cell arrest was significantly higher than that of LEN or ASA group. In combination, the expression of VEGF protein in MM1.S and RPMI-8226 cells was significantly down-regulated. The expression of 尾 -catenin protein and its downstream cyclin D1 protein were up-regulated in the nucleus of MM1.S and RPMI-8226 cells after 72 h of treatment with en, and the phosphorylation of 尾 -catenin in the cytoplasm was induced by ASA. The expression of 尾 -catenin protein in the nucleus decreased in the downstream of cyclin D1 protein. Conclusion: 1, aspirin and renalidomide have synergistic effect on inhibiting the proliferation of myeloma cells. Aspirin plays a synergistic role in inhibiting myeloma by down-regulating the expression of VEGF in myeloma cell line. Aspirin can promote the proliferation of myeloma cells by promoting the proliferation of myeloma cells. Cytoplasmic 尾 -catenin phosphorylation, In order to prevent 尾-catenin into the nucleus to play the role of chemosensitization of leinadamide.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R733.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 張根豪;劉俊文;蘇利沙;劉紅春;;阿司匹林對(duì)人卵巢癌組織和SKOV3細(xì)胞SOX7表達(dá)和Wnt/β-catenin信號(hào)通路的影響[J];鄭州大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2015年02期

2 劉厚琴;王毅;;WNT信號(hào)通路研究進(jìn)展[J];社區(qū)醫(yī)學(xué)雜志;2015年05期

3 周梅玲;陳雁;劉瑜;汪香;宋斌;;Ang-2及VEGF在多發(fā)性骨髓瘤中的表達(dá)及意義[J];現(xiàn)代腫瘤醫(yī)學(xué);2015年04期

4 王芳妹;楊子劍;韓梅;胡翔;丁小鳳;;阿司匹林對(duì)人慢性粒細(xì)胞白血病細(xì)胞株K562的生長(zhǎng)抑制作用[J];湖南師范大學(xué)自然科學(xué)學(xué)報(bào);2013年05期

5 李京佳;林相國(guó);許濤;徐萬(wàn)海;王曉民;;VEGF家族及其在腫瘤生長(zhǎng)中作用的研究[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2012年04期

6 李娟;張殿寶;羅紹凱;趙瑩;黃蓓暉;谷景立;;β-catenin在多發(fā)性骨髓瘤中的表達(dá)及其臨床意義[J];癌癥;2007年09期

7 李志;汪興洪;黃東平;張岱云;戴艷;;多發(fā)性骨髓瘤中內(nèi)皮抑素、一氧化氮與內(nèi)皮生長(zhǎng)因子表達(dá)的研究[J];華北煤炭醫(yī)學(xué)院學(xué)報(bào);2006年01期

8 王銀兒,胡盛壽,陳曦,叢祥鳳;阿司匹林對(duì)骨髓間充質(zhì)干細(xì)胞生長(zhǎng)的影響及可能的作用途徑[J];中國(guó)臨床康復(fù);2005年19期

9 弓娟琴;Fas介導(dǎo)的凋亡與caspase家族[J];國(guó)外醫(yī)學(xué).皮膚性病學(xué)分冊(cè);2001年05期

相關(guān)博士學(xué)位論文 前1條

1 丁江華;阿司匹林對(duì)多發(fā)性骨髓瘤的抗腫瘤效應(yīng)及其增強(qiáng)硼替佐米細(xì)胞毒作用的分子機(jī)制研究[D];南昌大學(xué);2014年

相關(guān)碩士學(xué)位論文 前1條

1 劉玉琴;阿司匹林對(duì)骨髓瘤細(xì)胞（MM1.S）增殖的影響及機(jī)制初步探討[D];南昌大學(xué)醫(yī)學(xué)院;2013年

，

本文編號(hào)：1951018