高胰岛素对MCF-7/ADR细胞化疗敏感性的影响

摘要

Objective To analyse the effects of high insulin on the expression and function of P-glycoprotein (P-gp), and preliminarily investigate the influence of insulin on chemotherapeutic sensitivity in MCF-7/ADR cells. Methods MCF-7/ADR cells were cultured with different concentrations of insulin(0.001, 0.005, 0.01, 0.05 and 0.1μmol/L). Real-time PCR was used to detect the expression of P-gp mRNA. Western blot assay was used to detect the expression level of P-gp. Rhodamine 123 was used to detect the efflux function level of P-gp. Cell viability and chemotherapeutic sensitivity were detected by MTT assay. Results High concentration of insulin (0.1 μmol/L) promoted the proliferation of MCF-7/ADR cells. The concentration of insulin (0.05 and 0.1 μmol/L) accelerated P-gp mRNA and protein expression, which also augmented the efflux function of P-glycoprotein and reduced the chemotherapeutic sensitivity to epirubicin. Conclusion High concentration of insulin may influence the drug resistance of breast cancer cells by promoting the expression and function of P-glycoprotein of MCF-7/ADR cells.%目的：分析高胰岛素对MCF-7/ADR细胞P-糖蛋白（P-gp）表达和功能的影响，并初步探讨胰岛素对MCF-7/ADR细胞化疗敏感性的影响。方法用不同胰岛素浓度（0.001、0.005、0.01、0.05、0.10μmol/L）的全细胞培养基干预MCF-7/ADR细胞，分别采用Real-time PCR法检测细胞中P-gp mRNA表达，Western Blot法检测细胞中P-gp蛋白表达水平，罗丹明123荧光实验测定P-gp的外排功能变化，MTT法检测MCF-7/ADR细胞活性及化疗敏感性。结果0.10μmol/L的胰岛素可促进MCF-7/ADR细胞增殖，0.05及0.10μmol/L浓度的胰岛素可增加MCF-7/ADR细胞P-gp mRNA及蛋白水平表达，并能增加P-gp的外排功能，降低MCF-7/ADR细胞对表阿霉素的化疗敏感性。结论高浓度胰岛素可能通过促进MCF-7/ADR细胞P-gp的表达和功能，增加乳腺癌细胞化疗耐药性，从而降低MCF-7/ADR细胞的化疗敏感性。