摘要
目的观察米非司酮体外逆转COC1/DDP细胞对顺铂的多药耐药性(MDR)以及对细胞葡萄糖神经酰氨合成酶(GCS)表达的影响,初步探讨其增敏机制。方法以米非司酮为MDR修饰剂,MTT法检测米非司酮对COC1/DDP的增敏效应。RT-PCR技术分析耐药株COC1/DDP的MDR逆转前后以及亲本株COC1细胞的GCS在mRNA水平的表达。结果米非司酮增强COC1/DDP细胞对DDP敏感性;与COC1相比,COC1/DDP细胞的GCS在mRNA水平的表达增强;米非司酮使GCS表达降低,效应呈剂量依赖关系。结论无毒性剂量米非司酮可以在体外增加卵巢癌COC1/DDP细胞对DDP的敏感性,作用机制与抑制GCS mRNA表达有关。
Objective To evaluate the effect of mifepristone in reversing multidrug resistance （MDR） and modulating glucosylceramide synthase （GCS） mRNA expression in human ovarian cancer COC1/DDP cells. Methods MDR cell line COC1/DDP was treated with mifepristone at different concentrations. The alterations in the chemosensitivity of the cells to cisplatin （DDP） were evaluated by MTT assay. GCS mRNA expression in COC1/DDP cells were detected using RT-PCR before and after mifepristone treatment. Results The expression level of GCS mRNA was 1.1792 in COC1/DDP cells, significantly higher than that in COC1 cells （0.2836）. Mifepristoneatl.25-10μmol/L increased the sensitivity of COC1/DDP cells to cisplatin, and inhibited GCS expression at the mRNA level, showing concentration-dependent modulation of MDR and gene expression in the cells. Conclusion Mifepristone can dose-dependently lower cisplatin resistance of COC1/DDP cells, the mechanism of which involves inhibition of GCS expression.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第9期1727-1730,共4页
Journal of Southern Medical University
