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机构地区:[1]福建中医药大学附属人民医院,福建福州350004
出 处:《中国医学创新》2016年第29期17-21,共5页Medical Innovation of China
基 金:福建省自然科学基金面上项目(2013J01324)
摘 要:目的:研究TRAIL联合顺铂对卵巢癌耐药细胞COC1/DDP生长的影响,以及联合用药对TRAIL死亡受体(DR4、DR5)、凋亡相关基因Smac、Survivin表达的影响,揭示TRAIL联合顺铂可能逆转COC1/DDP细胞耐药性的机制。方法:采用MTT法检测不同浓度TRAIL蛋白与DDP联合用药对COC1/DDP细胞生长的影响,用Annexin V-FITC法检测COC1/DDP细胞凋亡,用RT-PCR方法检测DDP对TRAIL受体(DR4、DR5)、凋亡相关基因Smac、Survivin表达。结果:TRAIL蛋白对COC1/DDP细胞生长有抑制作用,DDP与TRAIL蛋白联合作用后细胞生长抑制率显著升高(P<0.05)。DDP使COC1/DDP细胞的DR5表达水平显著增强,为正常对照组的3.45倍(P<0.001);Smac表达为对照组的2.82倍(P<0.001);DR4水平无明显变化;Survivin表达较对照组显著减少(P<0.001)。结论:TRAIL蛋白对COC1/DDP细胞生长有抑制作用,DDP与TRAIL联合增强了对COC1/DDP细胞生长抑制;TRAIL逆转COC1/DDP细胞对DDP的耐药性可能与DDP导致TRAIL受体DR5水平升高、Smac表达增加,通过线粒体途径促进了肿瘤细胞的凋亡有关。Objective:To investigate the effect of TRAIL combined with Cisplatin on the growth of ovarian cancer resistant COC1/DDP cells,and the effect of drug combination on the expression of TRAIL death receptors(DR4,DR5) and the apoptosis related genes Smac and Survivin.Method:The effects of different concentrations of TRAIL protein combined with DDP on the growth inhibition of COC1/DDP cells were detected by the MTT assay.Apoptosis of COC1/DDP cells was detected by V-FITC Annexin method.The expression of TRAIL death receptors(DR4,DR5) and the apoptosis related genes Smac,Survivin after treated with DDP were studied by RT-PCR technique.Result:TRAIL protein inhibited the growth of COC1/DDP cells,and the inhibition rate of DDP and TRAIL protein was significantly increased(P〈0.05).The COC1/DDP cell expression level of DR5 significantly enhanced as the control group of 3.45 times(P〈0.001).The expression of Smac for the control group of 2.82 times(P〈0.001).DR4 level without obvious change.Survivin expression compared with the control group decreased significantly(P〈0.001).Conclusion:TRAIL protein inhibited the growth of COC1/DDP cells,and the combination of DDP and TRAIL enhanced the inhibition of COC1/DDP cells.TRAIL reversing the drug resistance of COC1/DDP cells to DDP may cause by the increase of TRAIL receptor DR5 and Smac expression,and promote the apoptosis of tumor cells through the mitochondrial pathway.
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