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

GIAMBALVO GÓMEZ DILEYVIC; ACEBEDO MARTINEZ MACARENA; FERRAIOLO PAULA; REBAGLIATI CID ABRIL; MATERAZZI LOURDES; LOMBARDI MARÍA GABRIELA

Ciudad Autónoma De Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica/Sociedad Argentina de Inmunologia

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 inoncology. It has been reported that human breast cancer MCF-7 cells express muscarinicreceptors (MR) M3 and M4 subtypes and its activation promotes tumoral progression. Theaim of this work was to evaluate if intratumoral delivery of RNAi against M3 and M4 affectsthe growth kinetics of MCF-7 cells, in vivo. For this, cells treated with or without thecholinergic agonist carbachol (Carb, -8M), were injected subcutaneously in female Balb/cNUDE mice (1x107cells/0.2mL) that had been implanted with a 17β-estradiol pellet (1mg) aweek 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 tumoralvolume was estimated. After 38 days, all mice were sacrificed, the tumors were photographedand measured. The data analysis showed that tumors of cells stimulated with Carb had highergrowth kinetic and tumor volume compared to control group (day 38: 527.5±77.6 mm3 vs.740.5±72.8 mm3;p