CHEMORESISTANCE IN PANCREAS TUMOR MEDIATED BY SURVIVIN IN GEMCITABINE TREATMENT

SUSANA N. COSTANTINO; TOMÁS LOMBARDO; ELIDA ALVAREZ; CINTIA Y, MIHALEZ; MARIÁNGELES DÍAZ; MATIAS PIBUEL; MARTIN LEVERMANN; SILVINA LAURA LOMPARDÍA; DANIELA L. PAPADEMETRIO

Mar del Plata

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

Pancreatic adenocarcinomas are highly resistant to treatment. Gemcitabine (Gem) is the drug of choice with cytostatic effect on the tumor. Previous results indicate that during Gem treatment, levels of survivin raise, effect accompanied by an increase in basal autophagy.Previously, we saw that pharmacological inhibition of survivin was able to modulate the level of apoptosis after the treatment with Gem. From that, during the present study, we obtained a cell line knock down for survivin (MiaPaCa Surv - / -), in order to determine the effect of negative regulation on the sensitivity to Gem treatment in the presence or absence of 3-MA.We found that the cell line MiaPaCa Surv - / - established, showed low levels of survivin expression, without modifying the basal levels of apoptosis even after treatment with 3-MA (p>0.05). These results correlated with decreased levels of LC3-II in MiaPaCa Surv - / - vs MiaPaca WT determined by Western blot (p 0.05), while the WT line, inhibition of autophagy produces sensitizing cells to the pro-apoptotic action of Gem (p