1,25二羟维生素D3和塞莱昔布增强阿霉素对乳腺癌细胞株MCF/ADR的作用与NF-κB的关系

摘要

Objective To study the effect of lα ,25 -dihydroxyvitamin D3 associated with celecoxib affected doxorubicin on breast cancer cell line MCF/ADR via NF-KB. Methods MTT assay was used to detect MCF/ADR cells proliferation and half inhibitory concentration( IC50 ) of doxorubicin. MCF/ADR cell apoptosis, intracel- lular concentration of doxorubicin and cell surface P170 expression were determined by flow cytometry. The expression of P65 and IKBa was examined by immunohistochemistry. Results Administration of 1α,25-dihydroxyvitamin D3 50 x 10 -9 mol/L and celecoxib 25 x 10 -6 mol/L together inhibited MCF/ADR cells proliferation , induced cell apoptosis and increased cell sensitivity to doxorubicin. In addition, combination of these two drugs decreased P65 and P170 expression but increased IKBα expression in MCF/A- DR cells. Conclusion lα,25-dihydroxyvitamin D3 associated with celecoxib enhanced doxorubicin sensitivity of MCF/ADR cells which probably through inhibiting NF-KB and promoting cell apoptosis.%目的 研究1,25 二羟维生素D3(1,25-D)和塞莱昔布(CELE)影响阿霉素(ADM)对MCF/ADR细胞的作用与NF-κB的关系.方法 采用四唑氮蓝比色(MTT)法检测ADM的半数药物抑制浓度(IC50);采用流式细胞技术分析1,25-D和CELE对MCF/ADR细胞凋亡、细胞内ADM累积、P170表达的影响;免疫组化SP法检测1,25-D和CELE作用于MCF/ADR细胞后P65、IκBα表达水平.结果 1,25-D(50×10-9 mol/L)联合CELE(25×10-6 mol/L)和ADM作用后,MCF/ADR细胞凋亡率升高(P＜0.01),ADM的IC50显著降低(P＜0.01),P65和P170蛋白表达水平降低,IκBα表达增高(P＜0.01).结论 1,25-D联合CELE通过抑制NF-κB的活化、促进细胞凋亡从而增强ADM对耐药细胞的作用.