内源性途径调控芬太尼与5-氟尿嘧啶联合诱导的MCF-7乳腺癌细胞凋亡

The apoptosis in MCF-7 breast cancer cells through the intrinsic pathway induced by fentanyl in combination with 5-Fluouracil

目的探讨芬太尼与5-氟尿嘧啶(FU)联合应用对MCF-7乳腺癌细胞凋亡的影响及内源性途径的调控机制。方法作用48 h后通过流式细胞技术检测亚二倍体峰细胞凋亡情况,通过Western印迹检测Bcl-2、Bax表达情况。结果 1μmol/L及10μmol/L浓度的芬太尼单独应用均引起凋亡率增加(P<0.01),Bcl-2表达减弱(P<0.01),Bax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),Bcl-2表达减弱(P<0.01),Bax表达增强(P<0.01);三种浓度芬太尼与5-FU联合应用均具有协同作用(P<0.05,P<0.01)。结论一定浓度的芬太尼、5-FU及联合应用48h对MCF-7乳腺癌细胞有促进凋亡作用,并显著下调Bcl-2表达、上调Bax表达,两药联合应用启动内源性凋亡途径具有协同作用。

Objective To investigate the effects of fentanyl in combination with 5-Fluouracil( FU) on apoptosis and the regulation mechanism through the intrinsic pathway in MCF-7 breast cancer cells. Methods After treated with different concentration of fentanyl in combination with 5-FU for 48 h,the percentage of apoptotic cells was measured by FCM through sub DNA,and the expressions of Bcl-2 and Bax were detected by Western blot. Results The percentage of apoptosis and expression of Bax of MCF-7 breast cancer cells were increased significantly( P<0. 05,P<0. 01),while the expression of Bcl-2 was decreased significantly( P<0. 01),after treated with 1 μmol / L as well as10 μmol / L fentanyl alone. Similarly,the apoptosis rate and expression of Bax were also increased remarkablely( P<0. 01),while the expression of Bcl-2 was decreased remarkablely( P<0. 01),when cancer cells treated with 5-FU alone. Treated with different concentration of fentanyl combined with 5-FU,the apoptosis rate and expressions of Bcl-2 and Bax were promoted and demoted more remarkabely than those treated with two agents alone,including that there was a synergistic effects between fentanyl and 5-FU in induction of breast cancer cell apoptosis( P<0. 05,P<0. 01). Conclusions Certain concentration of fentanyl,5-FU and the combination of the two agents could promote apoptotosis of MCF-7 breast cancer cells by significant down-regulating expression of Bcl-2 and up-regulating expression of Bax and activation of the intrinsic pathways. Combination of fentanyl and 5-FU shows synergisms.