Cytostatic and antimigratory activity of repurposed hemostatic drug desmopressin against AVPR2-expressing human osteosarcoma cells

SOLERNÓ LM; SOBOL NT; PIFANO M; RIPOLL GV; VASQUEZ L; ALONSO DF; GARONA J

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica

Introduction.Osteosarcoma (OS) is the most common malignant primary bone tumor in children and young adults, with alarmingly elevated mortality rates. OS patients bear highly invasive and vascularized tumors, and are in urgent need of novel therapeutic strategies. Desmopressin (dDAVP) is a repurposed hemostatic drug in oncology that acts as a selective agonist for the AVPR2 receptor present in blood microvessels and several tumor types. dDAVP displayed cytostatic effects through canonical adenylate cyclase-cAMP-PKA axis activation in a wide variety of preclinical cancer models including breast and colorectal cancer, as well as a potent antiangiogenic and antimetastatic activity.Objectives.The aim of this work was to evaluate in vitro dDAVP antitumor activity in OS cells.Experimental design.The human OS cell lines MG-63 and U2-OS were used. AVPR2 expression was assessed by qPCR, and sensitivity to dDAVP was evaluated by in vitro proliferation and Transwell chemotaxis assays.Results.AVPR2 expression was detected in MG-63 cells but not in U2-OS. The presence of AVPR2 in MG-63 cells was confirmed by Western blot using MCF-7 breast cancer cells as a positive control. dDAVP showed significant cytostatic effects against exponentially growing MG-63 cell cultures after a 72-h exposure to the compound at 1 µM or higher (~30% inhibition; p