title: Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC.
abstract: We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles in the formation of multidrug resistance in cervical cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, China hongchendoc@163.com.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: F
authors.initials: F
authors.lastname: Zuo
mesh_terms: D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005964:Glucosyltransferases / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D015735:Mifepristone; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase