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

JABLOÑSKI, M.; RIVERO, E.M.; GARGIULO, L.; BRUZZONE, A.; LUTHY, I.A.

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC

Worldwide, breast cancer is the most diagnosed among women and it presents the highest mortality. In particular, the triple negative tumors,which do not express HER2 or hormonal receptors, lack specific treatment and have the worst outcome compared with the other subtypes. It has been described that β2-adrenergic receptors are overexpressed in claudin-low tumors. We have previously demonstrated that the β2 adrenergic agonist salbutamol (Salb) inhibited cell proliferation, migration, invasion and experimental metastases in MDA-MB-231 cells inoculated in NSG mice.The aim of the present investigation was to examine if Salb, which is broadly used for asthma treatment and has low toxicity, could be repurposed for thetreatment of breast cancer in order to improve the efficacy of classic therapies. To achieve this, we evaluated the effect on the proliferation of MDA-MB-231cells when co-incubated with Salb and chemotherapeutic agents such as paclitaxel (Pacli) or doxorubicin (Doxo).Proliferation of triple negative cancer cells MDA-MB-231 is significantly reduced when treated with the combination of Salb and either chemotherapeuticdrug. It is important to note that in both cases (Salb+Pacli and Salb+Doxo), the interaction between drugs was highly significant. This means that the inhibitionproduced by the combination is greater than the addition of the effects exerted when incubated separately. Moreover, when compared with the drugs alone, the cells were more detached from the plate, presented more events of apoptosis and showed lower numbers. Even if more experiments are needed to test other Combinations with adrenergic compounds, such as rauwolsine (Raw) or propanolol (Prop), and to assess the in vivo effect, these are encouragingresults.