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

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

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2018 vol. 233 p. 5949 - 5961

0021-9541

Ovarian cancer is the fifth leading cause of cancer-related deaths in women. In the past 20 years, the canonical types of drugs used to treat ovarian cancer have not been replaced and the survival rates have not changed. These facts show the clear 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 an ovarian cancer xenograft model. To achieve this goal, we analyzed the effect of the administration of DAPT alone and the co-administration of DAPT and recombinant 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 anticancer activity when co-administered with recombinant PDGFB. The administration of PDGFB alone normalized tumor vasculature by increasing periendothelial coverage and vascular functionality. Interestingly, this effect exerted by PDGFB was also observed in the presence of DAPT. Our findings suggest that PDGFB is able to improve 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.