DIFERENCIAL MODULATORY EFFECT OF NICOTINE ON THE RESPONSE OF TRIPLE NEGATIVE BREAST CANCER CELLS TO CONVENTIONAL OR METRONOMIC THERAPY

VASQUEZ ABIGAIL; SANCHEZ YAMILA; JALOM MAIA; ARIEL KAMINKER; FRANCISCO PEREZ KASTEN; ALEJANDRO ESPAÑOL

Congreso; LXVIII reunion anual de la Sociedad Argentina de Investigacion Clinica; 2023

Triple negative (TN) breast cancer is the subtype with the worst prognosis. In the conventional therapy (CT) the maximum tolerated dose of paclitaxel (PX) is used, which generates adverse effects requiring long drug-free intervals for patients´ recovery. An alternative strategy is metronomic therapy (MT) based on the administration of lower doses with short drug-free intervals. Previously we demonstrated that muscarinic receptors (MR) are expressed in breast tumor tissue but not in normal tissue, and that a metronomic combination of carbachol (Carb) (muscarinic agonist) with low doses of PX exerts an antitumoral effect. Breast tumor tissue also expresses nicotinic receptors (NR), and nicotine (NIC), the main active component of tobacco smoke, has been associated with the resistance to conventional oncologic treatment in lung cancer. The aim of this work is to evaluate if NIC differentially modulates the efficacy of the PX CT and the PX+Carb MT in TN breast cancer MDA-MB231 cells. By MTT assays we determined that NIC in a similar concentration to that of smoking patients´ plasma (10-7 M) increased the cell viability (basal:100+/-8.2%; NIC:147.8+/-13.6%). Although both CT (PX 10-7M) and MT (PX 10-8 M + Carb 10-11 M) decreased the cell viability (CT:67.2+/-3.2%; MT:73.6+/-3.0%), the presence of NIC only reduced the effectivity of CT (CT+NIC: 125.8+/-12.0%; MT+NIC: 63.6+/-6.1%, p