Markers of local and systemic estrogen metabolism in endometriosis

Abstract

OBJECTIVE: Dienogest (DNG) is a widely used progestin which is safe and effective for long-term management of endometriosis. However, its association to breast cells remains to be elucidated. We perform this study to investigate whether in vitro treatment of DNG can cause any biologic changes on MCF cell line (human estrogen receptor (ER)-positive breast cancer cell line) experiments.DESIGN: A laboratory study. MATERIALS AND METHODS: Following in vitro culture of MCF cells, we treated those cells and compared cell viability and the expression of several markers have shown to be increased in breast cancer cells between with estradiol alone and estradiol with DNG. Cell viability was measured utilizing MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and the expression of PCNA (proliferating cell nuclear antigen) and PAK4 (p21 activated kinase 4) was measured by western blot analyses. VEGF (vascular endothelial growth factor) and IL (interleukin)-32 were analyzed by ELISA, and MMP2 (matrix metalloproteinase 2) activity was assayed by zymography.RESULTS: In vitro treatment of MCF7 cells led to an increased cell viability by estradiol alone and decreased by both estradiol and DNG after 24 and 48-hour culture. The expression of PCNA after 48 hours showed the same result. VEGF and IL-32 were also significantly increased with estradiol and decreased following DNG treatment. However, there was no significant changes in MMP2 activity and PAK4 expression.CONCLUSIONS: These findings suggest that DNG may have inhibitory effects on carcinogenesis of breast cells by suppressing specific biologic changes treated by estradiol. However, further study is necessary using normal human breast cells.