# Anticancer Effects of BRD4 Inhibitor in Epithelial Ovarian Cancer

## TL;DR

This study shows that OPT-0139, a new drug targeting the BRD4 protein, can effectively reduce ovarian cancer cell growth and may work better when combined with chemotherapy.

## Contribution

OPT-0139 is a novel BRD4 inhibitor that demonstrates antitumor activity in ovarian cancer, both alone and in combination with cisplatin.

## Key findings

- OPT-0139 reduced ovarian cancer cell viability and proliferation while inducing apoptosis and cell cycle arrest.
- Combining OPT-0139 with cisplatin enhanced tumor suppression in both cell and animal models.
- BRD4 inhibition via OPT-0139 altered BRD4-related gene expression and suppressed tumor growth in xenograft models.

## Abstract

This study investigated a new drug, OPT-0139, an inhibitor of BRD4, a protein involved in ovarian cancer. OPT-0139 treatment reduced the growth and viability of ovarian cancer cells, induced cell death, and inhibited cancer cell division, suggesting its potential as a treatment agent. When combined with cisplatin, a chemotherapy drug, OPT-0139 was more effective in killing cancer cells and mitigating tumor growth. These findings suggest that OPT-0139, either alone or in combination with cisplatin, is a promising therapeutic agent for ovarian cancer.

Efforts have been made to develop bromodomain inhibitors as cancer treatments. Sub-pathways, particularly in ovarian cancer, affected by bromodomain-containing protein (BRD) remain unclear. This study verified the antitumor effects of a new drug that can overcome OPT-0139-chemoresistance to treat ovarian cancer. A mouse xenograft model of human ovarian cancer cells, SKOV3 and OVCAR3, was used in this study. Cell viability and proliferation were assessed using MTT and ATP assays. Cell cycle arrest and apoptosis were determined using flow cytometry. BRD4 and c-Myc expression and apoptosis-related molecules were detected using RT-PCR and real-time PCR and Western blot. We confirmed the OPT-0139 effect and mechanism of action in epithelial ovarian cancer. OPT-0139 significantly reduced cell viability and proliferation and induced apoptosis and cell cycle arrest. In the mouse xenograft model, significant changes in tumor growth, volume, weight, and BRD4-related gene expression were observed, suggesting the antitumor effects of BRD4 inhibitors. Combination therapy with cisplatin promoted apoptosis and suppressed tumor growth in vitro and in vivo. Our results suggest OPT-0139, a BRD4 inhibitor, as a promising anticancer drug for the treatment of ovarian cancer by inhibiting cell proliferation, decreasing cell viability, arresting cell cycle, and inducing apoptosis.