Desmopressin as a repositioning drug with potential antitumor effect in aggressive tumors of small cell lung cancer, prostate cancer and neuroblastoma.

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

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Drug repositioning offers the possibility of founding new moleculartargets using safe and effective known compounds. Desmopressinis a synthetic peptide agonist for vasopressin V2 receptor (V2r),used since decades for the treatment of urinary and hemostatic diseases.Our laboratory have been studying desmopressin as a repositioningdrug in oncology, showing their hemostatic and anti-tumorproperties in several tumor types. Neuroendocrine tumors (NET)comprise a heterogeneous group of neoplasms with a wide rangeof morphological and functional characteristics. Interestingly, a NEtransdifferentiation associated to the treatment has been detectedin prostate and lung tumor cells, showing therapy resistance, enhancedaggressiveness and poor prognosis. Similar features havebeen reported in neuroblastoma, a tumoral type that shares characteristicswith NET, such as specific neuropeptides and a variableaggressiveness. Moreover, the incidence of aggressive tumor withNE features is increasing and only few therapeutic alternatives areavailable. The aim of this work was to evaluate desmopressin effecton key events of the tumor development in human tumor celllines with NE features as PC-3 (PCa) and NCI-H82 (Small Cell LungCancer), and in cell lines of neuroblastoma as CHP-212 and SKN-AS. All cell lines express V2r and desmopressin showed in allcases a cytostatic effect measured by MTS assay. It also regulatesthe in vitro expression of the genes Bcl-2, Bcl-xL and BAX associatedto apoptosis, which were evaluated by RT-qPCR, promotinga pro-apoptotic balance in PC-3 and NCI-H82. Desmopressin alsoinhibited the PCa tumor growth in vivo by a 40% in a mouse xenograftmodel. These results evidence the desmopressin anti-tumorproperties on aggressive human NE cell lines and show, for the firsttime, the in vitro effect of desmopressin on neuroblastoma cell lines,recognizing it as a repositioning drug for the treatment of this type oftumors with few therapeutic alternatives.