Acción de agonistas y antagonistas alfa2-adrenérgicos sobre modelos in vivo de de cáncer de mama

BRUZZONE A; LANARI C; LUTHY IA

Buenos Aires

Congreso; VII Jornadas Multidisciplinarias de la Sociedad Argentina de Biología; 2005

Sociedad Argentina de Biología

We have already described that á2-adrenergic agonists enhance the proliferation of human and murine breast cancer cells in vitro at very low concentrations. They also stimulate the growth of several murine progestin-dependent tumors. The aim of this study was to evaluate the effect of á2-antagonists in vivo using a murine mammary carcinoma and a human breast cancer cell line growing in nude mice. CC4-3-HI tumors (progestin-independent mammary carcinomas) were inoculated s.c. in BALB/c female mice. After 24 hours they were separated randomly in 4 groups (n=x/gropu) and treated with clonidine (0.1 mg/kg daily), or rauwolscine (0.5 mg/Kg daily) or clonidine plus rawolscine or with vehicle. Tumors were measured daily. The specific á2-adrenergic agonist clonidine significantly stimulated CC4-3-HI tumor growth, as compared with control group; on day 28: 2339,4 ± 293,7 mm3 vs. 1299 ± 93,1 p<0.05. Rauwolscine, a specific antagonist, alone, reduced tumor growth (800,5 ± 218,8 mm3, p<0.05), and combined with the agonist reverted its stimulatory effect (1011,1 ± 206,8 mm3). The IBH-4 human breast cancer cell line was inoculated in sixteen nude mice, and after 24 hours the animals were treated with clonidine or vehicle. Clonidine showed a stimulatory effect in (on day 23: 13419,6 ± 909,4 vs 6868,7 ±1369,3 mm3, p<0.05). These results suggest that the á2-adrenergic antagonist rauwolscine could be used to inhibit breast cancer growth.