本文選題：乳腺癌 + 硫利達(dá)嗪��； 參考：《安徽醫(yī)科大學(xué)》2015年碩士論文

【摘要】：背景與目的乳腺癌是女性最常見的惡性腫瘤之一,其發(fā)病率逐年上升且趨向低齡化,尤以ER、PR及Her-2表達(dá)陰性的三陰乳腺癌惡性程度更高,預(yù)后較差,如何有效針對(duì)三陰乳腺癌的新藥研究成為目前乳腺癌治療的重點(diǎn)[1-2]。硫利達(dá)嗪為吩噻嗪衍生物,其被廣泛用于治療嚴(yán)重的精神和情緒障礙[3]。最新研究[4]證實(shí)硫利達(dá)嗪在體外可對(duì)抗多種腫瘤細(xì)胞活性,提示其可能作為一種新型抗癌藥物應(yīng)用于以后的腫瘤臨床治療。該研究以硫利達(dá)嗪作用于三陰乳腺癌MDA-MB-231細(xì)胞和乳腺癌MCF-7細(xì)胞,觀察硫利達(dá)嗪對(duì)人乳腺癌細(xì)胞MDA-MB-231和MCF-7的凋亡作用,并探討其機(jī)制。方法采用四甲基偶氮唑藍(lán)(MTT)法測(cè)定硫利達(dá)嗪對(duì)細(xì)胞的抑制作用,計(jì)算半數(shù)抑制濃度(IC50)。流式細(xì)胞術(shù)檢測(cè)硫利達(dá)嗪對(duì)細(xì)胞周期分布和凋亡的影響。比色法測(cè)定藥物對(duì)細(xì)胞Caspase-3活性的影響,Western blot法檢測(cè)凋亡調(diào)節(jié)蛋白Bcl-2,Bax表達(dá)的變化。結(jié)果硫利達(dá)嗪作用24 h后,MDA-MB-231、MCF-7細(xì)胞增殖明顯受到劑量依賴性抑制,其IC50分別為18、22μmol/L。流式細(xì)胞術(shù)結(jié)果顯示,隨著加入硫利達(dá)嗪濃度的提高,MDA-MB-231、MCF-7細(xì)胞均發(fā)生不同程度的G0/G1期阻滯,細(xì)胞凋亡程度的增加及伴隨胞內(nèi)Caspase-3活性的增加。各實(shí)驗(yàn)組與對(duì)照組比較,差異均有統(tǒng)計(jì)學(xué)意義(P0.01)。Western blot法結(jié)果顯示隨著藥物濃度的增加,抗凋亡蛋白Bcl-2下調(diào)、促凋亡蛋白Bax表達(dá)明顯上調(diào),各實(shí)驗(yàn)組與對(duì)照組相比,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。結(jié)論硫利達(dá)嗪對(duì)乳腺癌細(xì)胞MDA-MB-231、MCF-7具有顯著的增殖抑制作用,且可顯著誘導(dǎo)腫瘤細(xì)胞發(fā)生G0/G1期阻滯及凋亡,伴隨Caspase-3活性的上調(diào),其毒性機(jī)制可能與下調(diào)腫瘤細(xì)胞內(nèi)抗凋亡蛋白Bcl-2、上調(diào)Bax有關(guān)。
[Abstract]:Background & objective Breast cancer is one of the most common malignant tumors in women. The incidence of breast cancer increases year by year and tends to be younger. Especially, the malignant degree and prognosis of three-negative breast cancer with negative expression of ERPR and Her-2 are higher and worse. How to effectively study new drugs for Sanyin breast cancer has become the focus of breast cancer treatment [1-2]. Thirizine is a phenothiazine derivative, which is widely used in the treatment of severe mental and emotional disorders [3]. The latest study [4] confirmed that tiridamine could antagonize the activity of many kinds of tumor cells in vitro, suggesting that it may be used as a new anticancer drug for clinical treatment of cancer in the future. In this study, tri-negative breast cancer MDA-MB-231 cells and breast cancer MCF-7 cells were treated with tiridamine. The apoptosis of MDA-MB-231 and MCF-7 cells was observed and its mechanism was discussed. Methods the inhibitory effect of thiridamine on the cells was determined by MTT method and the half inhibitory concentration (IC50) was calculated. The effect of thiridamine on cell cycle distribution and apoptosis was detected by flow cytometry. Effect of drugs on the activity of Caspase-3 by colorimetric assay the expression of apoptosis-regulating protein Bcl-2nBax was detected by Western blot assay. Results the proliferation of MDA-MB-231 MCF-7 cells was inhibited in a dose-dependent manner after 24 h treatment with IC50 of 1822 渭 mol / L, respectively. The results of flow cytometry showed that with the increase of the concentration of thiridamine, MDA-MB-231 MCF-7 cells had different degrees of G0/G1 arrest, the degree of apoptosis and the increase of intracellular Caspase-3 activity. Compared with the control group, there were significant differences between the experimental group and the control group. The results of Western blot showed that with the increase of drug concentration, the anti-apoptotic protein Bcl-2 was down-regulated, and the expression of pro-apoptotic protein Bax was up-regulated, compared with the control group. The difference was statistically significant (P 0.01). Conclusion tiridazide can inhibit the proliferation of breast cancer cell line MDA-MB-231 and MCF-7, and induce G0/G1 phase arrest and apoptosis, accompanied by up-regulation of Caspase-3 activity. The mechanism of its toxicity may be related to the down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of Bax in tumor cells.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R737.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ZHANG XiaoSan;LI PengFei;MA WenJie;DI WenYu;ZHAO Shu;GAO QingZu;ZHAO YuYing;YANG MaoPeng;ZHANG QingYuan;;Risk factors of recurrence in small-sized, node negative breast cancer in young women: a retrospective study in Chinese population[J];Science China(Life Sciences);2013年04期

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本文編號(hào)：1933567