本文選題：NSCLC + A549��； 參考：《安徽醫(yī)科大學(xué)》2015年碩士論文

【摘要】：背景與目的:肺癌是嚴(yán)重危害人類健康的常見惡性腫瘤,化療是其重要治療手段之一,然而腫瘤耐藥的產(chǎn)生往往造成化療療效不佳。有研究發(fā)現(xiàn)抗凋亡蛋白Bcl-2家族的過表達(dá)參與了腫瘤的耐藥。在鉑類耐藥的肺癌患者,Bcl-2也過表達(dá)。本實驗研究Bcl-2抑制劑ABT-199■聯(lián)合卡鉑對人非小細(xì)胞肺癌細(xì)胞A549凋亡的增效作用。方法:四甲基偶氮唑藍(lán)(MTT)法檢測A BT-199和卡鉑不同濃度和作用時間對A 549細(xì)胞的增殖抑制作用并計算IC2Q作為聯(lián)合實驗參考劑量,檢測低劑量兩藥聯(lián)合作用24 h對A 549細(xì)胞的增殖抑制作用。流式細(xì)胞術(shù)(FCM)檢測ABT-199對A 5 4 9細(xì)胞周期的影響以及兩種藥物聯(lián)合作用下細(xì)胞凋亡率的變化;Western blot法檢測凋亡相關(guān)蛋白Bcl-2、Bax、Bcl-xl、Mcl-1、Caspase-3和Caspase-9的表達(dá)。結(jié)果:ABT-199和卡鉑對A549細(xì)胞有增殖抑制作用且呈時間和濃度依賴性,低劑量ABT-199聯(lián)合卡鉑的抑制率高于卡鉑單藥(P0.0l)。FCM結(jié)果顯示,隨著ABT-199濃度的升高,A549細(xì)胞發(fā)生不同程度的Go/G!期阻滯,聯(lián)合用藥組細(xì)胞凋亡率(72.4±2.2)%較卡鉑單藥組(37.3±1.8)°/。明顯增高。Western blot結(jié)果顯示,同單藥組相比,聯(lián)合用藥組細(xì)胞Bcl-2水平明顯下調(diào)(P0.01),Bcl-xl、Mcl-1無明顯變化,同時B ax水平增高,Caspase-3和Caspase-9活性增加(P0.01)。結(jié)論:ABT-199和卡怕均可有效抑制人非小細(xì)胞肺癌細(xì)胞系A(chǔ)549增殖,ABT-199可誘導(dǎo)細(xì)胞發(fā)生Go/G,期阻滯,對卡鉑誘導(dǎo)A 549細(xì)胞凋亡具有增效作用。
[Abstract]:Background & objective: lung cancer is a common malignant tumor that seriously endangers human health. Chemotherapy is one of the most important treatment methods. It has been found that the overexpression of anti-apoptotic protein Bcl-2 family is involved in tumor resistance. Bcl-2 is also overexpressed in patients with platinum-resistant lung cancer. The aim of this study was to investigate the synergistic effect of Bcl-2 inhibitor ABT-199 and carboplatin on apoptosis of human non-small cell lung cancer cell line A549. Methods: the inhibitory effects of BT-199 and carboplatin on the proliferation of A549 cells were measured by tetramethyl azolium blue tTassay. The IC2Q was used as the reference dose of the combined experiment, and the inhibitory effects of IC2Q and carboplatin on the proliferation of A549 cells were calculated. The inhibitory effect of low dose two drugs on proliferation of A549 cells for 24 h was detected. Flow cytometry (FCM) was used to detect the effect of ABT-199 on the cell cycle of A549 cells and the change of apoptosis rate under the combination of two drugs. The expression of apoptosis-related protein Bcl-2Bax-xlmcl-1mcl-1caspase-3 and Caspase-9 was detected by Western blot assay. Results the inhibition rate of low dose ABT-199 combined with carboplatin on A549 cells was higher than that of carboplatin single drug P0. 0 l).FCM. The results showed that with the increase of ABT-199 concentration, there were different degrees of Gor / GG in A549 cells. The apoptosis rate was 72.4 鹵2.2% in combination group and 37.3 鹵1.8 擄/ r in single carboplatin group. The results of Western blot showed that compared with the single drug group, the level of Bcl-2 in the combined treatment group was significantly decreased, while the activity of Caspase-3 and Caspase-9 was increased in the combined treatment group (P 0.01). Conclusion both 1: ABT-199 and Cabernet can effectively inhibit the proliferation of human non-small cell lung cancer cell line A549. ABT-199 can induce Go-G and phase arrest of A549 cells, which has a synergistic effect on the apoptosis of A549 cells induced by carboplatin.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R734.2

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相關(guān)期刊論文 前2條

1 李銀燕;王秀君;;鉑類抗癌藥物作用靶點及耐藥機(jī)制的研究進(jìn)展[J];中國細(xì)胞生物學(xué)學(xué)報;2013年07期

2 陳萬青;鄭榮壽;曾紅梅;鄒小農(nóng);張思維;赫捷;;2011年中國惡性腫瘤發(fā)病和死亡分析[J];中國腫瘤;2015年01期

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本文編號：1795511