芬太尼与5-氟尿嘧啶联合应用对MCF-7乳腺癌细胞增殖与细胞周期的影响

摘要

Objective To investigate the effects of different concentration of fentanyl along with 5-FU on the proliferation and cell cycle in MCF-7 breast cancer cells.Methods MTT was applied for evaluation of the antiproliferative inhibitive effects 24, 48 and 72 h after incubation.Moreover, the effect of cell cycle was evaluated by flow cytometry (FCM) 48 h after incubation.Results When using fentanyl alone, the average IR was increased significantly in all three groups (P<0.05), compared with that of untreated group .When using fentanyl combined with 5-FU, the significant synergy was observed in all three groups 48 h or 72 h after incubation(P<0.05).Whereas the IR was positively correlated with the concentration of fentanyl .When using fentanyl alone , along with increasing of the concentration of fentanyl , the rate of G0/G1 phase cell was increased (P<0.05), the rate of S phase cell was decreased (P<0.05), and the PI reduction was also calculat-ed(P<0.05).When using fentanyl combined with 5-FU, the rate of G0/G1 phase cell was increased(P<0.05), nevertheless,the rate of S&G2M phase cells was decreased, as well as PI (P<0.05).Whereas, significant synergy was revealed in all three groups , for the reduc-tion of G2M phase cells rat and PI (P<0.05).Conclusions Fentanyl in certain concentration , 5-FU and the combination of the two have antiproliferative effect on MCF-7 breast cancer cells .Using fentanyl combined with 5-FU, the synergisms is related with the G 0/G1 blockage by morphine and the S blockage by 5-FU, which is decreased the rate of cells in G 2/M phase.In addition, the dose-and time-dependent manners is also shown in a certain extent .%目的：研究芬太尼与5-氟尿嘧啶（ FU）联合应用对人乳腺癌细胞（ MCF-7）增殖与细胞周期的影响。方法药物作用24、48、72 h后噻唑蓝（ MTT）法测定MCF-7乳腺癌细胞的增殖抑制情况，选取48 h，通过流式细胞技术（ FCM）检测细胞周期情况。结果增殖抑制情况：芬太尼单独应用时，与未处理组相比，均引起平均增殖抑制率（IR）增加（P＜0.05）；三种浓度的芬太尼与5-FU联合应用作用48、72 h时，均具有协同作用（P＜0.05）；平均IR随着其中芬太尼浓度增加依次增加。细胞周期影响：单独应用芬太尼处理时，G0／G1期细胞比例随着芬太尼浓度的增加依次增加（P＜0.05），S期比例依次降低（P＜0.05），增殖指数（PI）亦依次降低。联合用药时，G0／G1期细胞比例随其中芬太尼浓度的增加依次增加（P＜0.05）， S期、G2／M期细胞、PI随芬太尼浓度的增加依次降低（P＜0.05）；三种浓度芬太尼与5-FU联合应用，在对 G2／M期细胞比例和 PI减少方面均具有协同作用（P＜0.05）。结论一定浓度的芬太尼、5-FU及联合应用对MCF-7乳腺癌细胞有增殖抑制作用，两药联合应用，既抑制了 G0／G1期到 S期的转化，又抑制了S期向G2／M期的转化，可显示出协同作用。并且对增殖抑制和细胞周期的影响也与芬太尼的浓度有一定的剂量-时间依赖关系。