不同浓度吗啡与5-氟尿嘧啶联合应用通过Fas途径诱导MCF-7乳腺癌细胞凋亡的体外研究  

The vitro study on the apoptosis of MCF-7 breast cancer cells induced by different concentration of morphine in combination with 5-fluouracil through the Fas pathway

作　　者：王志学[1] 刘新伟[1] 李汝泓[1] 雷燕[2] 闫彩云[1] 李桂银 

机构地区：[1]承德医学院附属医院麻醉科,067000 [2]承德医学院附属医院手术室,067000 [3]河北省隆化县中医院麻醉科,068150

出　　处：《实用医学杂志》2013年第8期1212-1214,共3页The Journal of Practical Medicine

基　　金：承德市科学技术研究与发展计划项目(编号:201121037)

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。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 ceils 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 ceils by significant up-regulating expression of Fas and Caspase-8 and activation of the extrinsic pathways. Combination of morphine and 5-FU showed synergisms.

关 键 词：吗啡 5-氟尿嘧啶 MCF-7 凋亡 FAS CASPASE-8 

分 类 号：R737.9[医药卫生—肿瘤]