JQ-1, a BRD4 inhibitor, was found to effectively suppress ocular melanoma growth by inducing G1 cell cycle arrest, according to new study results. The combination of BET bromodomain inhibition and SWI/SNF complex knockdown enhanced the effect on tumor-bearing mice.

Researchers observed phenotypes resulting from gene knockdown and synergistic effects with BRD inhibitor treatment and SWI/SNF complex knockdown. Flow cytometry was used to analyze the effects of JQ-1 on the cell cycle and apoptosis in ocular melanoma cell lines. RNA sequencing was performed to explore the mechanism of BRD4, according to results published in Investigative Ophthalmology & Visual Science.

JQ-1 exhibited the best tumor inhibitory effect among the tested inhibitors. Specifically:

• Cell Viability and Colony Formation: JQ-1 significantly decreased the viability and colony formation of MEL270 cells. The inhibitory effect of JQ-1 was more pronounced than that of BRD4 knockdown, suggesting JQ-1 acts on multiple targets beyond BRD4.
• Synergistic Effects: The combination of JQ-1 with SWI/SNF complex inhibitors (BRG1 and BRD9) showed synergistic inhibitory effects on cell viability and colony formation.
• In Vivo Efficacy: In a xenograft model with NOG/scid mice, JQ-1 treatment led to a significant reduction in tumor volume and weight compared to the control group.
• Mechanism of Action: JQ-1 induced G1 cell cycle arrest in ocular melanoma cell lines, including MEL270, MEL290, CRMM1, and CRMM2. RNA sequencing identified 17 differentially expressed genes downregulated by JQ-1, with TP53I11, SH2D5, SEMA5A, and MDGA1 positively correlated with BRD4. Low expression of these genes improved overall and disease-free survival rates in patients.

"Although the experimental results have confirmed the inhibitory effect of JQ-1 on ocular melanoma, further studies on the pathogenesis of ocular melanoma and the mechanism of JQ-1 are still needed to promote the further applications of JQ-1 in tumors," noted researchers.

They reported having no conflicts of interest.