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Onco Targets Ther. 2012;5:335-42. doi: 10.2147/OTT.S36098. Epub 2012 Nov 9.

A study of mifepristone/IFN-γ-induced apoptosis of human cholangiocarcinoma cell line FRH-0201 in vitro.

Author information

  • 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.

Abstract

OBJECTIVE:

To investigate the effects of mifepristone, a progesterone receptor (PR) antagonist, through the proliferation of human cholangiocarcinoma cell line FRH-0201 in vitro and the possible mechanisms involved.

METHODS:

A two-step addition of poly-HRP anti-mouse immunoglobulin G detection system was used to detect the expression of PR in FRH-0201 cells. After treatments with various concentrations of mifepristone (10, 20, 40, 80, 160, and 320 μmol/L) at various time intervals (24, 48, and 72 hours), the rate of cell inhibition, the rate of cell apoptosis, and the expression of bax/bcl-2/Fas were analyzed with tetrazolium blue (MTT) assay, flow cytometry, reverse transcription polymerase chain reaction and Western blotting. The effect of mifepristone and mifepristone combined with interferon (IFN)-γ-inducing apoptosis on the cells was observed.

RESULTS:

Mifepristone remarkably inhibited the proliferation of FRH-0201 cells, which was revealed by MTT assay in a dose- and time-dependent manner. The inhibitory rate gradually increased following the increase of the dosage of mifepristone from a low dosage (10 μmol/L) to a high dosage (320 μmol/L) at different time intervals. Flow cytometry analysis showed mifepristone increased the rate of the FRH-0201 cell-line apoptosis. Notably, the rate of apoptosis increased markedly when the cells were pretreated with IFN-γ and then treated with mifepristone. In addition, mifepristone obviously upregulated bax and Fas expression and downregulated bcl-2 expression.

CONCLUSION:

Mifepristone effectively inhibited the growth of PR-positive human cholangiocarcinoma cell line FRH-0201 in vitro through multiple mechanisms. Mifepristone combined with IFN-γ might therefore induce the apoptosis of the cell line, which is possibly a beneficial clinical scheme for patients suffering from cholangiocarcinoma.

KEYWORDS:

IFN-γ; apoptosis; cholangiocarcinoma; mifepristone; progesterone

PMID:
23180967
[PubMed]
PMCID:
PMC3497892
Free PMC Article

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