Dienogest, a
synthetic progestin, has been shown to be effective against
endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells.
Decorin has been shown to be a powerful endogenous
tumor repressor acting in a paracrine fashion to limit
tumor growth. Our objectives were to examine the direct effects of
progesterone and
dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how
decorin contributes to this effect. We also examined DCN
mRNA expression in 50
endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both
decorin and
dienogest. Using a
chromatin immunoprecipitation assay, it was noted that
progesterone and
dienogest directly induced the binding of the
decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells).
Progesterone and
dienogest also led to significant induced cell cycle arrest via
decorin by promoting production of p21 in both cell lines in a dose-dependent manner.
Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN
mRNA expression in patients treated with
dienogest was higher than that in the control group. In conclusion,
decorin induced by
dienogest appears to play a crucial role in suppressing
endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.