新型光敏剂联合阿霉素对乳腺癌细胞增殖及周期的影响

The Effect of New Photosensitizer Combined with Adriamycin on Cell Proliferation and Cell Cycle

目的:研究新型光敏剂叶绿素衍生物(Chlorophyl derivative4,CPD4),联合阿霉素对人乳腺癌MCF-7细胞增殖及周期的影响,初步探讨联合用药的作用机制,为临床开辟新的治疗方法提供实验依据。方法:以人乳腺癌MCF-7细胞系为研究对象,新型光敏剂和乳腺癌传统化疗药物阿霉素(ADM)联合给药。采用流式细胞仪检测ADM组(2个浓度组分别预处理24小时、48小时)、光动力效应组、联合用药组细胞凋亡率和周期分布;流式细胞仪分析ADM(20ng/mL)预处理24小时、48小时对细胞平均荧光强度的影响以及ADM预处理24小时、48小时后加入CPD4 1.5μg/mL孵育不同时间细胞平均荧光强度的变化。结果:联合用药组细胞凋亡率明显高于单药组,差异有统计学意义(P<0.01);光动力效应可造成MCF-7细胞G_0/G_1期阻滞,低浓度ADM预处理后G_2/M期细胞增加,联合用药时G_2/M期细胞升高。ADM预处理MCF-7细胞24小时、48小时细胞平均荧光强度与对照组荧光强度比较差异无统计学意义(P>0.05);ADM预处理MCF-7后能增加光敏剂CPD4进入细胞的量,在CPD4孵育2小时细胞平均荧光强度最强,且ADM预处理48小时组>预处理24小时组>对照组。结论:ADM预处理MCF-7细胞后能够增加光敏剂CPD4进入细胞的量;光动力效应联合ADM具有协同作用。

Objective： To study the effect of new photosensitizer Chlorophyl-derivative （CPD4） combined with Adriamycin on cell cycle and cell proliferation of MCF-7 breast cancer cell line and to investigate the mechanism of combination therapy. Methods： A new type of photosensitizer and traditional chemotherapy drug Adriamycin （ADM） were used to treat breast cancer cell line MCF-7. Flow cytometry was employed to detect apoptosis rate and cell cycle distribution in ADM group, group with photodynamic effect and the combined group. The influence of ADM on the mean fluorescence intensity and the changes in the mean fluorescence intensity after CPO4 （1.5μg/mL） treatment were analyzed. Results： The apoptosis rate of the combination group was higher than that in the other two groups, with statistical significance （P〈0.01）. Photodynamic effect caused G0/G1 phase arrest in MCF-7 cells. Low concentration of ADM increased the number of G2/M phase cells. The percentage of G2/M phase cells was increased in the combination group. No significant difference was found in the mean fluorescence intensity between ADM pretreated MCF-7 cells for 24 hours and 48 hours and the control group （P〉0.05）. Pretreatment of MCF-7 cells with ADM increased the volume of photosensitizer CPD4 into the cells. The mean fluorescence intensity at 2 hours after CPD4 incubation was the highest. Conclusion： ADM can increase the amount of CPD4 into the MCF-7 cells. Photodynamic therapy com bined with Adriamycin has a synergistic effect on MCF-7 cells.