UOXETINE AND SERTRALINE TREATMENT PREVENTS STRESS-INDUCED ALTERATIONS IN TUMOR CELL CYCLE PROTEINS RELATED TO ENHANCED TUMOR PROGRESSION IN EL4 LYMPHOMA. PARTICIPATION OF THE IMMUNE SYSTEM.

HELENA ANDREA STERLE; ANA MARÍA GENARO; MARÍA EMILA DI ROSSO; GRACIELA A CREMASCHI

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC, SAIB, SAI, SAA, SAB, SAB, SAFE, SAFIS, SAH, SAP

Selective serotonin reuptake inhibitors, as fluoxetine (F) and sertraline(S), are frequently used for the treatment of stress-associateddisorders. However, there is contradictory evidence about theireffect on the immune system and cancer prognosis. We have previouslyreported that both F and S are able to revert chronic stressenhancement of EL-4 lymphoma growth. In the present work westudied the effect of F or S on chronic stress-induced alterations intumor cell cycle progression and in the anti-tumor immunity. FemaleC57BL/6J mice were treated with of F or S and subjected (E) or not(C) to a heterotrophic chronic stress for five weeks. Then, mice weresubcutaneously injected with EL4 T lymphoma cells to generate asolid tumor. Tumor mRNA expression of proteins related to regulationand promotion of cell cycle was assessed by qRT-PCR. mRNAlevels of cyclins A2, D1 and D3 were increased in tumor from E micecompared to C (P<0.01). In addition, cell cycle inhibitors p15, p16,p21 and p27 mRNA levels were decreased in tumors from E animalscompared to C (P<0.01). Both F and S treatment resulted in C valuesof mRNA expression of these regulatory proteins. To determinethe involvement of alterations in anti-tumor immune response in thestress-induced tumor growth, adoptive transfer experiments wereperformed. For this purpose, irradiated animals were tail vein injectedwith lymphoid cells of C and E animals treated or not with F andS and then inoculated with tumor cells. Data indicated that tumorgrowth was increased in mice injected with lymphocytes from E miceas compared to those transferred with immune cells from C animals.Furthermore, mice injected with immune cells from E animals treatedwith F and S did not show this effect. These results suggest thatantidepressant treatment prevents stress induced tumor growth byavoiding chronic stress effects on the antitumor immunity.