Abstract 5883: Phosphodiesterase 7-A is a novel potential therapeutic target against ovarian cancer

Ovarian cancer (OC) is the leading cause of gynecologic cancer-related deaths due to late diagnosis and chemoresistance. RNA-seq data, conducted in collaboration with our group, compared the expression of transcription levels between normal Fallopian tube and high-grade serous ovarian carcinoma samples and revealed phosphodiesterase 7-A as a novel potential therapeutic target against the disease. Metabolic cell viability assays (MCV) were conducted following OC cells treatment with selective PDE7 inhibitor (BRL50481) in monotherapy or in association with paclitaxel (PTX). Mechanism of action of the drug was evaluated by cell cycle analysis, anexina V/PI assay, immunoblotting, real-time PCR and scanning/transmission electron microscopy. Data showed that the use of the BRL50481 in monotherapy reduced A2780 cells MCV by ~60% in a dose-dependent manner after 48h treatment, but nothing significant was observed in OVCAR3. On the other hand, the association of BRL50481 and PTX promoted inhibition of MCV in both cell lines analyzed. An increase in the potency of PTX was also observed, an aspect verified with the reduction of its IC50 in relation to monotherapy by 30% (p