Effect of selective serotonin reuptake inhibitors on chronic stress-induced immunomodulation and molecular alterations related to EL-4 lymphoma invasion in C57BL/6J mice

GENARO AM; GONZALEZ-MURANO MR; DI ROSSO ME

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Reunion Anual de la Sociedad de Inmunología (SAI), XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE),VII Reunión Anual de la Sociedad Argenti; 2016

SAIC, SAFE,SAI

Chronic stress is involved in the onset of specific psychiatricdiseases such as major depression. Fluoxetine 􀀊F􀀋 and sertraline􀀊S􀀋, t􀁙o selective serotonin reupta􀁍e inhibitors, are 􀁙idely used forthe treatment of depressive symptoms of cancer patients althoughthere are contradictory evidences about its effects on immunity andneoplastic processes. 􀀹e have previously reported that both F orS are able to revert chronic stress enhancement of EL􀀏􀀖 lymphomagro􀁙th and of spontaneous metastasis. 􀀫n the present 􀁙or􀁍 􀁙estudied the effect of F or S on chronic stress􀀏induced reduction inT cell proliferation and molecular alterations related to cell invasion.Female C􀀗􀀙􀀤L/􀀘􀀬 mice 􀁙ere subjected 􀀊E􀀋 or not 􀀊C􀀋 to a heterotrophicchronic stress model for five 􀁙ee􀁍s. Chronic administration ofF or S reverted chronic stress􀀏induced decrease in T cell proliferationto the selective mitogen Con A evaluated by 􀀽􀀕H􀀿􀀏thymidineincorporation 􀀊􀀫nteraction stress x drug, p􀀞􀀒.􀀒􀀗, n􀀟􀀖􀀋. Moreover,F or S 􀁙ere able to enhance T cell proliferation compared to Canimals 􀀊p􀀞􀀒.􀀒􀀗, n􀀟􀀖􀀋. After five 􀁙ee􀁍s of chronic stress exposureand chronic administration of F or S, mice􀁙ere subcutaneouslyinjected 􀁙ith EL􀀏􀀖 T lymphoma cells to generate a solid tumor.Chronic administration of F or S reverted chronic stress􀀏inducedincrease in MMP-2 and MMP-9 mRNA levels in the solid tumorsevaluated by q􀀴T􀀏􀀲C􀀴 􀀊􀀫nteraction stress x drug, p􀀞􀀒.􀀒􀀗 andp􀀞􀀒.􀀒􀀒􀀓 respectively, n􀀟􀀖􀀋. Furthermore the reduction in 􀀯􀀯􀀲sinhibitors TIMP-1 and TIMP-2 mRNA levels observed in E mice,􀁙as reverted by both F or S 􀀊􀀫nteraction stress x drug, p􀀞􀀒.􀀒􀀗 andp􀀞􀀒.􀀒􀀓 respectively, n􀀟􀀖􀀋. These results suggest that chronic antidepressanttreatment prevents enhanced tumor evolution by reversingT􀀏cell impairment and tumor cell invasion capacity. 􀀱ur gro􀁙ingunderstanding of novel pharmacological actions of these drugsprovides ne􀁙 perspectives in cancer therapy.