Evaluation of Schedule-Dependent Effects of Chemotherapy in vitro and one in vivo retinoblastoma model

URSULA WINTER; NEGROTTO , SOLEDAD; MONTERO CARCABOSO ANGEL ; MENA AGUSTINA ; GUILLERMO CHANTADA ; PASCO-PASCUAL GUILLEM ; SUÑOL MARIONA ; SCHAIQUEVICH PAULA

Mar del Plata

Congreso; XLVIII Reunion Annual de la Sociedad Argentina de Farmacología Experimental.; 2016

Sociedad Argentina de Farmacología Experimental.

Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The effect t of metronomic chemotherapy treatment has not been assessed for retinoblastoma and may aid to decrease the incidence of adverse events by using lower doses. Our aim was to evaluate the cytotoxic and antiangiogenic effect of chemotherapy used in the clinics using different in vitro and in vivo models. Two patient-derived retinoblastoma cell types (007 and 008) and two human vascular endothelial cell types (HUVEC and EPC) were exposed to increasing concentrations of melphalan or topotecan in a conventional (single dose) or metronomic (7-day exposure) treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50) was determined by MTT. The effect of treatments on endothelial cells was assessed by the ability of tube formation using matrigel assay. We also evaluated the in vivo response to conventional and metronomic topotecan in a retinoblastoma xenograft model. We compared the vascular density of tumors after treatments using CD31.Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after the two treatments schemes. Whereas the IC50 for melphalan and topotecan significantly decreased after metronomic compared to conventional treatment in endothelial and 008 cells (p0.05). Metronomic topotecan or melphalan significantly inhibited in vitro tube formation in HUVEC and EPC compared to vehicle treated cells (p