P糖蛋白对高能X射线照射后Cyt-c释放和caspase-3活性的影响

目的 探讨抗P-gp单抗UIC2对X射线照射后不同时间肿瘤细胞凋亡、细胞内cytochrome c（Cyt-c）释放和caspase-3活性的影响。方法 以抗P-gp单抗UIC2抑制P-gp功能，X射线照射P-gp表达的乳腺癌耐药细胞MCF-7／Adr。运用流式细胞仪检测X射线照射后细胞凋亡、细胞内Cyt-c和caspase-3活性的变化。结果 X射线照射后6、12和24h应用UIC2抑制P-gp功能组细胞凋亡显著增加（P〈0．01），胞浆cyt-c的表达均明显高于对照组（P〈0．05），胞内caspase-3活性均显著高于对照组（P〈0．01）。结论 抑制P-gp功能，增加了Cyt-c释放和caspase-3活性，提示P-gp对X射线照射后肿瘤细胞胞浆cyt-c释放和caspase-3活性均有抑制作用。

The inhibition effect of P-glycoprotein on cytochrome c release and caspase-3 activation by X-ray irradiation.

Objective To investigate the effects of P-glycoprotein (P-gp) on cytochrome c (Cyt c)release and caspase-3 activation in drug-resistant tumor cell after X-ray irradiation. Methods Anti-P-gp McAb UIC-2 was applied to block P-gp function. MCF-7/Adr, P-gp-overexpressed drug-resistant breast cancer cell line, was irradiated by X-rays. Flow cytometry was used to measure apoptosis, dynamic changes of mitochondrial cytochrome c release and caspase-3 activation at various time after X-ray irradiation. Results Both the expression of cyt c and the activation of caspase-3 in P-gp-blocked group were up-regulated significantly, compared with those in control group at 6 h, 12 h, and 24 h after X-ray irradiation, respectively. Conclusion The current study showed that inhibition of P-gp function can increase cytochrome c release and caspase-3 activation.It suggested that P-gp inhibits X-ray induced cytochrome c release and caspase-3 activation. ;