EFFECT OF DOXORUBICIN AND PACLITAXEL IN COMBINATION WITH THE BETA2 ADRENERGIC AGONIST SALBUTAMOL ON BREAST CANCER MDA-MB-231 CELL PROLIFERATION

JABLOÑSKI M; BRUZZONE A; RIVERO E; LÜTHY IA; GARGIULO L

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

We have previously described (SAIC 2015, abstract 008)that the beta2 adrenergic agonist salbutamol (Salb) inhibited cellmigration, invasion and experimental metastases in MDA-MB-231cells inoculated in NSG mice. Also (SAIC 2015, abstract 538)that beta2-adrenergic receptors are overexpressed in claudin-lowtumors. The goal of the present investigation was to evaluate ifSalb, which toxicity is low, could be repurposed for the treatmentof breast cancer. For this, we evaluated the effect of co-incubationof salbutamol with chemotherapy agents to diminish their effectiveconcentrations. Human breast cancer MDA-MB-231 cells wereincubated for 2 days with DMEM-F12 medium with 2% Fetal CalfSerum in the presence or absence (control) of doxorubicin (Doxo,100 pM, 1, 100 nM) or paclitaxel (Pacli, 10, 100 pM, or 1 nM) w ithor without Salb (10, 100 nM or 1 uM). Cell proliferation was performedby [3H]-thymidine incorporation and statistical analysis bytwo-way ANOVA. The effect of Doxo +/- Salb on cell proliferationwas analyzed. As an example, 100 nM Salb alone inhibited 50.9+/- 1.23 % cell proliferation. When incubated with Doxo 100 pM,the inhibition was 37.1 +/- 5.10 %, representing a 42% reductionwith respect to Doxo alone. When analyzed by two-way ANOVA,the effect of both Doxo and Salb was highly significant (p