Intratumoral gene silencing of muscarinic receptors by RNA interference decrease human breast cancer cells growth.

FERRAIOLO, PAULA; LOMBARDI, GABRIELA; GIAMBALVO, DILEYVIC; REBAGLIATI CID, ABRIL; ACEBEDO, MACARENA; MATERAZZI, LOURDES

CABA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Intratumoral gene silencing of muscarinic receptors by RNA interference decrease human breast cancer cells growth.Giambalvo Dileyvic, Acebedo Macarena, Paula Ferraiolo, Rebagliati Cid Abril, Materazzi Lourdes, Lombardi María Gabriela.The ability of interfering RNA (RNAi) to silence target genes with high efficiency and specificity has stimulated efforts to develop these molecules as therapeutic agents in oncology. It has been reported that human breast cancer MCF-7 cells express muscarinic receptors (MR) M3 and M4 subtypes and its activation promotes tumoral progression. The aim of this work was to evaluate if intratumoral delivery of RNAi against M3 and M4 affects the growth kinetics of MCF-7 cells, in vivo. For this, cells treated with or without the cholinergic agonist carbachol (Carb, -8M), were injected subcutaneously in female Balb/c NUDE mice (1x107cells/0.2mL) that had been implanted with a 17β-estradiol pellet (1mg) a week earlier. After 5 days, mice had small visible tumors and were divided into groups: MCF-7 cells (control) and MCF-7+Carb (RNAi once, RNAi repeated (once a week, four times) and without RNAi). Tumor diameter were measured three times per week and the tumoral volume was estimated. After 38 days, all mice were sacrificed, the tumors were photographed and measured. The data analysis showed that tumors of cells stimulated with Carb had higher growth kinetic and tumor volume compared to control group (day 38: 527.5±77.6 mm3 vs. 740.5±72.8 mm3;p