PDGFB as a vascular normalization agent in an ovarian cancer model treated with a gamma-secretase inhibitor

PAZOS, MARIA C.; SEQUEIRA, GONZALO; BOCCHICCHIO, SEBASTIAN; MAY, MARIA; ABRAMOVICH, DALHIA; PARBORELL, FERNANDA; TESONE, MARTA; IRUSTA, GRISELDA

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2018

0021-9541

Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Inthe past 20 years, the canonical types of drugs used to treat ovarian cancer havenot been replaced and the survival rates have not changed. These facts show theclear need to find new therapeutic strategies for this illness. Thus, the aim of the present study was to investigate the effect of a gamma-secretase inhibitor(DAPT) in combination with the Platelet-derived growth factor B (PDGFB) on anovarian cancer xenograft model. To achieve this goal, we analyzed the effect ofthe administration of DAPT alone and the co-administration of DAPT andrecombinant PDGFB on parameters associated with tumor growth and angiogenesis in an orthotopic experimental model of ovarian cancer. We observed that the dose of DAPT used was ineffective to reduce ovarian tumor growth, but showed anticanceractivity when co-administered with recombinant PDGFB. The administration of PDGFBalone normalized tumor vasculature by increasing periendothelial coverage andvascular functionality. Interestingly, this effect exerted by PDGFB was alsoobserved in the presence of DAPT. Our findings suggest that PDGFB is able toimprove tumor vascularity and allows the anticancer action of DAPT in the tumor. We propose that this therapeutic strategy could be a new tool for ovarian cancer treatment and deserves further studies