Effect of Estrogen Receptor β agonists on proliferation and gene expression of ovarian cancer cells

Estrogen receptor (ER) b affects ovarian carcinogenesis. We examined the effects of four ERβ agonists on proliferation and gene expression of OVCAR3 and OAW-42 cells.

OVCAR3 and OAW-42 ovarian cancer cells were treated with the ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol and cell growth was measured by means of the Cell Titer Blue Assay (Promega). Proliferation was examined after knockdown of ERβ using specific siRNA. Transcriptome analyses were performed with these cell lines after treatment with ERB-041, WAY200070 and Liquiritigenin by means of Affymetrix GeneChip arrays.

After treatment of OVCAR3 and OAW-42 cells with the ERβ agonists, a significant decrease of proliferation was observed in both cell lines even at a low concentration of 10 nM. Maximum effects were induced by Liquiritigenin, which inhibited growth of OVCAR3 cells down to 68,8% after 5 days of treatment, and ERB-041 suppressing proliferation by about 30%. In OAW-42 cells, the agonist WAY200070 induced maximum effects and inhibited cell growth down to 73,2%, whereas ERB-041 decreased proliferation down to 75,6% after 5 days of treatment. On the other hand, knockdown of ERβ with specific siRNA increased cell growth of OVCAR3 cells by 45%. Transcriptome analyses revealed a set of genes regulated after addition of ERb agonists. EPCAM gene, known to be upregulated in ovarian cancer, was 2,2-fold downregulated after treatment in OAW42 cells.

In conclusion, the observed growth-inhibitory effects of all ERβ agonists on ovarian cancer cell lines in vitro encourage further studies to test its possible use in the clinical setting.