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


CONCLUSIONS
Mifepristone can dose-dependently lower cisplatin resistance of COC(1)/DDP cells, the mechanism of which involves inhibition of GCS expression.
Liu
Ying
Y
Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital, Guangzhou, China.
Wang
Li-li
LL
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005964:Glucosyltransferases / Q000235:genetics*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D002945:Cisplatin