Effect of clonidine on murine mammary carcinomas induced by MPA

BRUZZONE A; LANARI C; LUTHY IA

Buenos Aires

Congreso; V Jornadas Multidisciplinarias de la Sociedad Argentina de Biología; 2003

Sociedad Argentina de Biología

We have described that catecholamines enhance proliferation of hu­man breast cells in vitro at very low concentrations, an effect mediated by á2-adrenergic receptors. The purpose of this study was to evaluate the effect of the a2 agonist, cloni­dine, on tumor growth in a murine model of breast cancer. The CC4-2-HD (progestin-dependent) tumor was inoculated s.c to female BALB/c mice without medroxyprogesterone acetate (MPA). Simultaneously, clonidine group was injected with 0.1 mg/kg daily. Control group received vehicle. Tumor size was measured with a caliper. Clonidine stimulated tumor growth significantly, as compared with control group (i.e. at day 6: 504 ± 64 mm3 vs. 203 ± 35, p=0.00043). Nevertheless, tumor regression was observed in both groups after 12 days, suggesting that clonidine alone is not sufficient to support tumor growth. No effect was seen for clonidine neither in CC4-2-HD tumor treated with MPA depot, nor on progestin independent tumor (C7-HI), as compared with control groups, suggesting that in this tumor model the effect of clonidine is modulatory of growth induced by MPA. The effect of this agonist on cell proliferation was also studied in primary cultures of tumors derived from animal treated with MPA or with MPA plus clonidine. In vitro incubation with clonidine induced a gaussian increase in 3H-thymidine incorporation with a maximum at 1 nM (158 ± 17.1 % from the value without clonidine) for tumors treated with MPA, and 1 pM (189 ± 33.0 %) for tumors treated with MPA plus clonidine, suggesting an increased sensitivity in tumors receiving the drug. The widespread utilization of clonidine in the treatment of hypertension and in the management of hot flashes in breast cancer survivors highlight the importance of the study of the effect of this drug in the growth of mammary tumor in different experimental models.