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目的研究白藜芦醇对乳腺癌MDA-MB-231阿霉素(adriamycin,ADR)耐药细胞株化疗敏感性的影响。方法建立阿霉素耐药细胞株MDA-MB-231/ADR。MTT法检测白藜芦醇作用对MDA-MB-231、MDA-MB-231/ADR细胞阿霉素化疗敏感性的影响,统计半数细胞死亡药物浓度(IC50值)。流式细胞术检测白藜芦醇对阿霉素诱导MDA-MB-231/ADR细胞凋亡的影响,Western blot法检测Bcl-2、Bax、cleaved-caspase3、肝细胞生长因子受体CMet、P-糖蛋白(P-glycoportein,P-gp)的表达。结果成功建立阿霉素耐药株MDA-MB-231/ADR,其IC50值为8.79±0.96μg/ml,较MDA-MB-231细胞IC50值(0.24±0.03μg/ml)有显著差异,P<0.01。5μM、15μM白藜芦醇对MDA-MB-231细胞阿霉素敏感性没有影响,但显著增强MDA-MB-231/ADR细胞阿霉素敏感性,15μM组IC50值下降为3.46±0.58μg/ml,有显著性差异,P<0.01。5μM、15μM白藜芦醇均增加阿霉素诱导MDA-MB-231/ADR的细胞凋亡;15μM白藜芦醇处理组,Bcl-2表达显著降低,Bax、cleaved-caspase3表达显著升高。5μM、15μM白藜芦醇处理显著降低耐药基因C-Met、P-gp的表达。结论白藜芦醇增加阿霉素耐药株MDA-MB-231/ADR对阿霉素的敏感性,可能的作用机制为降低耐药基因C-Met、P-gp的表达。
Objective To study the effect of resveratrol on the chemosensitivity of breast cancer cell line MDR-231-adriamycin (ADR). Methods Adriamycin resistant cell line MDA-MB-231 / ADR was established. The effects of resveratrol on the chemosensitivity of doxorubicin to MDA-MB-231 and MDA-MB-231 / ADR cells were detected by MTT assay. The IC50 value of the drug was calculated. The apoptosis of MDA-MB-231 / ADR cells induced by doxorubicin was detected by flow cytometry. The expressions of Bcl-2, Bax, cleaved-caspase3, CMet, P - P-glycoportin (P-gp) expression. RESULTS: Adriamycin-resistant MDA-MB-231 / ADR cells were successfully established with IC50 of 8.79 ± 0.96μg / ml, which was significantly different from that of MDA-MB-231 cells (0.24 ± 0.03μg / ml) <0.01.5μM, 15μM resveratrol had no effect on the doxorubicin sensitivity of MDA-MB-231 cells, but significantly increased the doxorubicin sensitivity of MDA-MB-231 / ADR cells, IC50 decreased to 3.46 ± 0.58μg / ml, P <0.01.5μM, 15μM resveratrol increased the apoptosis of MDA-MB-231 / ADR induced by doxorubicin; 15μM resveratrol treatment group, Bcl-2 The expression of Bax and cleaved-caspase3 was significantly decreased. Resveratrol treatment with 5μM and 15μM significantly decreased the expression of C-Met and P-gp. Conclusion Resveratrol increases the sensitivity of doxorubicin-resistant MDA-MB-231 / ADR to doxorubicin. The possible mechanism is that resveratrol can decrease the expression of C-Met and P-gp.