The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines

Abstract

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Keywords: GPER receptor; fallopian tubes; ovarian cancer; therapeutic.

Figure 1

DMSO tolerance. FT190 (A), OV90 (B) and OVCAR420 (C) were examined against the indicated DMSO concentrations.

Figure 2

G-1 dose–response curves. G-1 concentration–response curves for FT190 (A), OV90 (B) and OVCAR420 (C). Estimated IC50 values were 2.58, 1.06 and 6.97 μM for FT190, OV90 and OVCAR420, respectively. Incubation was for 48 h.

Figure 3

Effect of GPER on migration. (A–C) Migration assays were performed using FT190, OV90 and OVCAR420 cells treated with the G-1 agonist for 12 h. Data are presented as the mean ± SEM for three separate experiments. * p < 0.05 vs. control, ** p < 0.005 vs. control. Statistical analyses were performed using ANOVA followed by Dunnett’s post hoc test.