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芬太尼与5-氟尿嘧啶联合诱导MCF-7乳腺癌细胞凋亡及其机制

The Apoptosis in MCF-7 breast cancer cells induced by fentanyl in combination with 5-Fluouracil and the mechanism
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摘要 目的研究芬太尼与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、外源性途径的调控机制。方法作用48 h后通过流式细胞技术(FCM)检测Annexin V-EGFP/PI染色的细胞凋亡情况,通过免疫细胞化学检测Bcl-2、Bax、Fas表达情况。结果单独应用芬太尼时1μmol/L与10μmol/L浓度组凋亡率均增加(P<0.05,P<0.01),Bcl-2表达减弱(P<0.05,P<0.01)、Bax表达增强(P<0.01)、Fas表达增强(P<0.01);单独应用500μmol/L 5-FU后凋亡率亦明显增加(P<0.01),Bcl-2表达减弱(P<0.01)、Bax、Fas表达增强(P<0.01);联合应用芬太尼与5-FU,协同作用在3组均显现(P<0.05,P<0.01)。结论芬太尼、5-FU在一定浓度范围内单独或联合应用可促进MCF-7乳腺癌细胞凋亡,并使Bcl-2表达下调,Bax、Fas表达上调。联合应用两类药物可能在内源性、外源性途径调控细胞凋亡上显示协同效应。 Objective To investigate the effects of fentanyl in combination with 5-FU on apoptosis and the regulation mechanism of the intrinsic and extrinsic pathways 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 Annexin V-EGFP / PI staining,and the expressions of Bcl-2,Bax and Fas were detected by immunocytochemistry. Results After treated with 1 μmol / L as well as 10 μmol / L of fentanyl alone,the percentage of apoptosis and expressions of Bax and Fas were increased significantly( P<0. 05,P<0. 01),while the expression of Bcl-2 was decreased significantly( P<0. 05,P < 0. 01). Similarly,the apoptosis rate and expressions of Bax and Fas also were increased remarkably( P <0. 01),but the expression of Bcl-2 was decreased significantly( 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 Bax and Fas were increased more remarkably than those treated with two agents alone( P<0. 01),meanwhile the expression of Bcl-2 was decreased significantly( P<0. 01),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 apoptosis of MCF-7 breast cancer cells,which result from 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 effects.
出处 《中国老年学杂志》 CAS CSCD 北大核心 2015年第23期6705-6707,共3页 Chinese Journal of Gerontology
关键词 芬太尼 5-氟尿嘧啶 MCF-7 凋亡 Bcl-2 BAX FAS Fentanyl 5-Fluouracil MCF-7 Apoptosis Bcl-2 Bax Fas
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