【摘要】 目的:研究吗啡与5-FU联合应用对MCF-7乳腺癌细胞凋亡的影响及Fas途径的调控机制。方法:作用48h后通过流式细胞技术(FCM)检测亚二倍体峰细胞凋亡情况,通过WesternBlot检测Fas、Caspase-8表达情况。结果:250μmol/L及1250μmol/L浓度的吗啡单独应用均引起凋亡率增加(P<0.01),Fas、Caspase-8表达增强(P<0.05,P<0.01);5-FU单独应用后凋亡率亦明显增加(P<0.01),Fas、Caspase-8表达增强(P<0.01);三种浓度吗啡与5-FU联合应用,均具有协同作用(P<0.05,P<0.01)。Caspase-8与Fas表达变化呈显著正相关(r=0.854,P<0.01)。结论:一定浓度的吗啡、5-FU及联合应用48h对MCF-7乳腺癌细胞有促进凋亡作用,并更为显著上调Fas表达和Caspase-8活性,两药联合应用启动外源性凋亡途径具有协同作用。更多还原

【Abstract】 Objective To investigate the effects of morphine in combination with 5-Fu on apoptosis and the regulation mechanism through Fas pathway in MCF-7 breast cancer cells.Methods After treated with different concentration of morphine in combination with 5-Fu for 48 h,the percentage of apoptotic cells was measured by FCM through subDNA,and the expression of Fas and Caspase-8 were detected by western blotting.Results The percentage of apoptosis and expression of Fas and Caspase-8 of MCF-7 breast cancer cells were increased significantly(P < 0.05,P < 0.01) after treated with 250 μmol /L and 1 250 μmol /L of morphine alone.Similarily,the apoptosis rate and expression of Fas and Caspase-8 also increased remarkablely when cancer cells treated with 5-FU alone(P < 0.01).Treated with different concentration of morphine combined with 5-FU,the apoptosis rate and expression of Fas and Caspase-8 increased more remarkable than that treated with two agents alone(P < 0.05,P < 0.01),indicating that there is a synergistic effects between morphine and 5-FU in induction of breast cancer cell apoptosis.meanwhile,the data also showed that there was positive correlation between the expression of Fas and activity of caspase-8(r = 0.854,P < 0.01).Conclusion Certain concentration of Morphine,5-FU and the combination of the two agents could promote apoptotosis of MCF-7 breast cancer cells by significant up-regulating expression of Fas and Caspase-8 and activation of the extrinsic pathways.Combination of morphine and 5-FU showed synergisms.更多还原