Effect of vasopressin analogs on angiogenesis and neuroendocrine differentiation in aggressive prostate cancer

RODRÍGUEZ RB; SOBOL NT; SOLERNÓ LM; GARONA J; ALONSO DF; RIPOLL GV; PIFANO M

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica

Prostate cancer (PC) is the second cause of cancer-related death inmales worldwide. Invariably after treatment, disease progressesinto a castration-resistant PC (CRPC) which implies no therapyresponse and poor prognosis. This tumor progression correlateswith a loss of epithelial characteristics (EMT), promoting metastaticprogression and development of cell foci with neuroendocrinedifferentiation (NED). Angiogenesis is a key factor for PCprogression and has been linked with NED and androgendeprivation therapy. For years, our group has studied desmopressin(dDAVP), a first generation vasopressin (AVP) analog, agonist of V2receptor (AVPR2) and [V4Q5]dDAVP, a second generation analogwith enhanced cytostatic activity. Both peptides showedantiproliferative effects in vitro and in vivo on several tumor modelsincluding aggressive PC and, interestingly, reduced the expressionof NE markers. Given this evidence, and the increasing incidence ofaggressive PC with NE features, this work aims to evaluate theeffect of AVP analogs on key processes related to cancerprogression on aggressive NE PC-3 model. The cells were treatedwith AVP analogs for 7 days, subsequently studying its effect on theexpression of NE markers and genes associated to EMT by RT-qPCR,and the sensitivity to the chemotherapeutic agent Cisplatin wasmeasured by MTS assays. Sustained exposure to analogs reducedthe NE markers expression, and modulated the expression of genesassociated to EMT in vitro. Furthermore, we assessed angiogenesisin vivo with Matrigel® plug modified assay in nude mice. Treatmentwith each analog reduced PC-3 cell-induced angiogenic response bynearly 50 % versus control. These results position AVP analogs aspotential and interesting angiostatic agents, with the abi lity tomodulate aggressiveness for CRPC, a disease with few therapeuticalternatives