P糖蛋白功能抑制对耐药肿瘤细胞MCF-7/Adr放射敏感性的影响

目的 探讨P糖蛋白(P-gp)对肿瘤细胞放射敏感性的调控效应。方法 以经与未经维拉帕米处理的MCF-7/Adr细胞分别作为抑制和对照组,运用流式细胞仪检测X射线照射后不同时间点细胞凋亡率和线粒体膜电位(ΔΨm)的动态变化。结果 抑制组细胞在X射线照射后6、12、24h细胞凋亡率分别是25.53%±2.85%、30.43%±2.21%、39.03%±2.60%,对照组分别是16.13%±1.16%、21.73%±1.31%、27.53%±2.55%;抑制组在6、12、24h的ΔΨm平均荧光强度值分别是75.27±4.90、96.47±5.59、57.77±2.55,对照组分别是54.17±4.05、62.30±5.93、39.53±2.65。各时间点抑制组的细胞凋亡率和ΔΨm平均荧光强度值均明显高于对照组(P<0.01)。抑制组经X射线照射后24h细胞凋亡率最高(F=47.870,P=0.000)。照射后12h平均荧光强度值最高(F=74.485,P=0.000)。结论 抑制MCF-7/Adr细胞的P-gp功能上调了细胞的放射敏感性,这可能与线粒体膜电位改变有关。

Effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells

Objective To observe the effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells. Methods Flow cytometry was used to examine the dynamic changes of apoptosis rate and mito- chondrial membrane potential (ΔΨm) in verapamil-treated and untreated MCF-7/Adr cells after the X-ray exposure. Results The apoptotic rate of verapamil-treated cells was 25.53%±2.85%, 30.43%±2.21%, 39.03%±2.60% at 6, 12, and 24 h after X-ray exposure, respectively, and was 16.13%±1.16%, 21.73%±1.31% and 27.53%±2.55% for the untreated cells. The mean fluorescence intensity of verapamil-treated cells was 75.27±4.90, 96.47±5.59, 57.77±2.55 responding time points, in comparison with the intensity of 54.17±4.05, 62.30±5.93, and 39.53±2.65, for the untreated cells were significantly higher than those in the untreated cells at each of the specified time point (P<0.01), and in the former cells, the apoptosis rate reached the maximum at 24 h (F=47.870, P=0.000) and the ΔΨm at 12 h after X-ray exposure (F=74.485, P=0.000). Conclusion The radiosensitivity of MCF-7/Adr cells is increased after functional inhibition of p-glycoprotein, possibly in relation to the alteration of ΔΨm.