ADDITION OF β-BLOCKER PROPRANOLOL OR ANTIPARASITIC DRUG IVERMECTIN ENHANCES METHOTREXATE ANTICANCER ACTIVITY IN HUMAN OSTEOSARCOMA CELLS

SOLERNÓ LM; SOBOL NT; GOTTARDO MF; CHANTADA G; ALONSO DF; GARONA J

Mar del Plata

Congreso; Reunión de Sociedades de Biociencia 2021; 2021

Sociedad Argentina de Investigación Clínica

Osteosarcoma (OS) is considered a clinical challenge due to itsrapid progression and limited response to therapy. Despite being afirst-line therapeutic strategy for OS, methotrexate (MTX), speciallyat high doses, can cause significant toxicity, including myelosup-pression, nephro- and hepatotoxicity. In this context, the addition ofcost-effective repurposed agents such as the non-selective β-block-er propranolol (PPN) or the antiparasitic drug ivermectin (IVM),could potentiate the therapeutic anticancer activity of MTX in OS, atlower and better tolerated doses.The aim of this work was to evaluate the in vitro antitumoral activityof MTX in combination with PPN or IVM on highly aggressive MG-63and U-2OS human OS cells.Sensitivity to PPN, IVM and MTX was assessed obtaining IC50 val-ues of 45.6 μM, 8.3 μM and 8.6 nM for MG-63 and 47 μM, 12.8μM, and 58.6 nM for U-2OS cells, respectively. After 72h treatments,exponential growth of OS cells was significantly abrogated aftercombining different optimal and suboptimal concentrations of bothPPN or IVM plus MTX. However, stronger synergistic cytostatic ef-fects (CI