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[米非司酮调节卵巢癌细胞中葡萄糖神经酰胺合酶的表达并逆转多药耐药性]

[Mifepristone modulates glucosylceramide synthase expression and reverse multidrug resistance in ovarian cancer cells].

作者信息

Liu Ying, Wang Li-li

机构信息

Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital, Guangzhou, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2008 Aug;28(9):1727-30.

PMID:18819906
Abstract

OBJECTIVE

To evaluate the effect of mifepristone in reversing multidrug resistance(MDR) and modulating glucosylceramide synthase (GCS) mRNA expression in human ovarian cancer COC(1)/DDP cells.

METHODS

MDR cell line COC(1)/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 COC(1)/DDP cells were detected using RT-PCR before and after mifepristone treatment.

RESULTS

The expression level of GCS mRNA was 1.1792 in COC(1)/DDP cells, significantly higher than that in COC(1) cells (0.2836). Mifepristone at 1.25-10 micromol/L increased the sensitivity of COC(1)/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 COC(1)/DDP cells, the mechanism of which involves inhibition of GCS expression.

摘要

目的

评估米非司酮对人卵巢癌COC(1)/DDP细胞多药耐药性(MDR)的逆转作用及对葡糖神经酰胺合酶(GCS)mRNA表达的调节作用。

方法

用不同浓度的米非司酮处理多药耐药细胞系COC(1)/DDP。采用MTT法评估细胞对顺铂(DDP)化疗敏感性的变化。在米非司酮处理前后,用RT-PCR检测COC(1)/DDP细胞中GCS mRNA的表达。

结果

COC(1)/DDP细胞中GCS mRNA表达水平为1.1792,显著高于COC(1)细胞(0.2836)。1.25 - 10 μmol/L的米非司酮增加了COC(1)/DDP细胞对顺铂的敏感性,并在mRNA水平抑制了GCS表达,显示出对细胞多药耐药性和基因表达的浓度依赖性调节。

结论

米非司酮可剂量依赖性降低COC(1)/DDP细胞对顺铂的耐药性,其机制涉及抑制GCS表达。

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