Combination Hormonal Drug Therapy Inhibits <i>In Vitro</i> Growth of Adult Ovarian Granulosa Tumor Cells

This study investigated the mechanism of action and <i>in vitro</i> efficacy of an anti-hormonal combination drug regimen in treating adult-type granulosa cell tumors of the ovary (AGCT). Using patient-derived and commercial AGCT cell lines, the IC₅₀ values of bicalutamide, anastrozole, and leuprolide acetate were established alone and in combination via cell proliferation assays. Averaged across cell lines, IC₅₀ was determined for bicalutamide (IC₅₀: 7.3 µM) and anastrozole (IC₅₀: 6.2 µM). Minimal effect was seen with leuprolide acetate alone. Suppression of proliferation was increased with the combination of an antiandrogen and an aromatase inhibitor. RNA was extracted from treated and untreated cells. RNA sequencing of cells treated with both anastrozole and darolutamide suggested downregulation of pathways involved in DNA synthesis, cell cycle regulation, and chromosomal organization. MHC I activity and DNA damage response were upregulated. This anti-hormonal drug regimen for AGCT merits prospective investigation.