EFFECT OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS ON CHRONIC STRESS-INDUCED IMMUNOMODULATION AND MOLECULAR ALTERATIONS RELATED TO EL-4 LYMPHOMA INVASION IN C57BL/6J MICE o

DI ROSSO MARÍA EMILIA; GONZÁLEZ MURANO MARÍA ROSA; GENARO ANA MARÍA

Mar del Plata

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); 2016

SAIC SAI SAFE AACYTAL

Chronic stress is involved in the onset of specific psychiatric diseases such as major depression. Fluoxetine (F) and sertraline (S), two selective serotonin reuptake inhibitors, are widely used for the treatment of depressive symptoms of cancer patients although there are contradictory evidences about its effects on immunity and neoplastic processes. We have previously reported that both F or S are able to revert chronic stress enhancement of EL-4 lymphoma growth and spontaneous metastasis. In the present work we studied the effect of F or S on chronic stress-induced reduction in T cell proliferation and molecular alterations related to cell invasion. Female C57BL/6J mice were subjected (E) or not (C) to a heterotrophic chronic stress model for five weeks. Chronic administration of F or S reverted chronic stress-induced decrease in T cell proliferation to the selective mitogen Con A evaluated by [3H]-thymidine incorporation (Interaction stress x drug, p<0.05). Moreover, F or S were able to enhance T cell proliferation compared to C animals (p<0.05). After five weeks of chronic stress exposure and chronic administration of F or S, mice were subcutaneously injected with EL-4 T lymphoma cells to generate a solid tumor. Chronic administration of F or S reverted chronic stress-induced increase in MMP-2 and MMP-9 mRNA levels in the solid tumors evaluated by qRT-PCR (Interaction stress x drug, p<0.05 and p<0.001 respectively). Furthermore the reduction in MMPs inhibitors TIMP-1 and TIMP-2 mRNA levels observed in E mice, was reverted by both F or S (Interaction stress x drug, p<0.05 and p<0.01 respectively). These results suggest that chronic antidepressant treatment prevents enhanced tumor evolution by reversing T-cell impairment and tumor cell invasion capacity. Our growing understanding of novel pharmacological actions of these drugs provides new perspectives in cancer therapy.