Mifepristone inhibits extracellular matrix formation in uterine leiomyoma.

Abstract

OBJECTIVE:

To characterize the efficacy of mifepristone treatment on extracellular matrix (ECM) production in leiomyomas.

DESIGN:

Laboratory study.

SETTING:

University research laboratory.

PATIENT(S):

None.

INTERVENTION(S):

Treatment of human immortalized two-dimensional (2D) and three-dimensional (3D) leiomyoma and myometrial cells with mifepristone and the progestin promegestone (R5020).

MAIN OUTCOME MEASURE(S):

Expression of COL1A1, fibronectin, versican variant V0, and dermatopontin in treated leiomyoma cells by Western blot analysis and confirmatory immunohistochemistry staining of treated 3D cultures.

RESULT(S):

Treatment with progestin stimulated production of COL1A1, fibronectin, versican, and dermatopontin. Mifepristone treatment inhibited protein production of these genes, most notably with versican expression. Combination treatment with both the agonist and antagonist further inhibited protein expression of these genes. Immunohistochemistry performed on 3D cultures demonstrated generalized inhibition of ECM protein concentration.

CONCLUSION(S):

Our study demonstrated that the progesterone agonist R5020 directly stimulated extracellular matrix components COL1A1, fibronectin, versican, and dermatopontin production in human leiomyoma cells. Progesterone antagonist mifepristone decreased protein production of these genes to levels comparable with untreated leiomyoma cells.

• Authors: Amrita Patel, Minnie Malik, Joy Britten, Jeris Cox, William H Catherino
• Journal: Fertility and sterility (Fertil Steril) Vol. 105 Issue 4 Pg. 1102-10 (Apr 2016) ISSN: 1556-5653 [Electronic] United States
• PMID: 26776909 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Hormone Antagonists
• Mifepristone
• Promegestone

Topics

• Cell Line, Transformed
• Dose-Response Relationship, Drug
• Extracellular Matrix (drug effects, genetics, metabolism)
• Female
• Hormone Antagonists (pharmacology)
• Humans
• Leiomyoma (genetics, metabolism, pathology)
• Mifepristone (pharmacology)
• Promegestone (pharmacology)
• Tumor Cells, Cultured
• Uterine Neoplasms (genetics, metabolism, pathology)