不同浓度吗啡与5-氟尿嘧啶联合应用对MCF-7乳腺癌细胞增殖凋亡的影响

Effects of different concentrations of morphine in combination with 5-Fluouracil on the proliferation and apoptosis in MCF-7 breast cancer cells

目的研究吗啡与5-氟尿嘧啶(5-FU)联合应用对MCF-7乳腺癌细胞增殖和凋亡的影响。方法药物作用24、48、72 h后MTT法测定MCF-7乳腺癌细胞的增殖抑制情况,选取48 h,通过流式细胞技术检测亚二倍体峰细胞凋亡情况。结果增殖抑制情况:吗啡单独应用时,平均抑制率(IR)随着吗啡浓度的增加依次增加;作用24、48 h时,250μmol/L及1 250μmol/L浓度的吗啡对增殖具有抑制作用(P<0.05);作用72 h时,各浓度组均对增殖有抑制作用(P<0.05)。5-FU单独应用时,作用24、48、72 h时均对增殖具有抑制作用(P<0.05)。吗啡与5-FU联合应用时,平均IR亦随着其中吗啡浓度的增加依次增加;作用24 h时,3种浓度的吗啡与5-FU均无协同作用(P>0.05);作用48、72 h时,3种浓度的吗啡与5-FU联合应用,均具有协同作用(P<0.05)。凋亡情况:吗啡单独应用时,凋亡率随着吗啡浓度的增加依次增加,与未处理组相比,250μmol/L及1 250μmol/L浓度的吗啡均引起凋亡率增加(P<0.05)。5-FU单独应用时,凋亡率亦明显增加(P<0.05)。吗啡与5-FU联合应用时,凋亡率亦随着其中吗啡浓度的增加依次增加;3种浓度的吗啡与5-FU联合应用,均具有协同作用(P<0.05)。结论一定浓度的吗啡、5-FU及联合应用对MCF-7乳腺癌细胞有增殖抑制作用,且与吗啡的浓度有一定的剂量依赖关系,两药联合应用48 h和72 h,可显示出协同作用。一定浓度的吗啡、5-FU及联合应用48 h对MCF-7乳腺癌细胞有促进凋亡作用,且与吗啡的浓度有一定的剂量依赖关系,两药联合应用具有协同作用。

Objective To investigate the effects of different concentrations of morphine in combination with 5-Fluouracil（5-FU） on the proliferation and apoptosis in MCF-7 breast cancer cells.Methods MTT was applied for evaluation of the proliferation inhibitive effects of morphine in combination with 5-FU 24 h,48 h and 72 h after incubation.Moreover,the apoptosis rate was evaluated with flow cytometry（FCM） 48 h after incubation.Results When using morphine alone,the IR of proliferation inhibitive effect was positively correlated with the concentration of morphine;whereas the proliferation was significantly inhibited by morphine of 250 and 1 250 μmol/L 24 h or 48 h after incubation,and also by morphine in all concentraions 72 h after incubation（P0.05）.When using 5-FU alone,the proliferation was significantly inhibited by 5-FU in all concentrations 24 h,48 h or 72 h after incubation（P0.01）.When using morphine combined with 5-FU,the IR was also positively correlated with the concentration of morphine;whereas significant synergy was observed 48 h or 72 h after incubation（P0.05）.When using morphine alone,the apoptosis rate was positively correlated with the concentration of morphine,with significant difference revealed in 250 μmol/L and 1 250 μmol/L groups when comparing with controls（P0.01）.When using 5-FU alone,the apoptosis rate was also significantly raised（P0.01）.When using morphine combined with 5-FU,the apoptosis rate was also positively correlated with the concentration of morphine,whereas significant synergy was revealed（P0.05）.Conclusion Morphine in certain concentration presents synergic effect in combination with 5-FU on anti-proliferation and apoptosis in MCF-7 breast cancer cells.