IFN β sensitizes and INFα protecs pancreatic tumor cells against the proapoptotic effect of gemcitavine by modulating autophagy

MIHALEZ C; DIAZL M; LOMPARDIA S; LEVERMAN MARTIN; PIBUEL M; HAJOS S; PAPADEMETRIO D; COSTANTINO S; LOMBARDO T; ALVAREZ E

Congreso; Congreso de Socieadas Medicas; 2017

SAIC- SAI- SAFE

Infiltrating ductal adenocarcinoma of the pancreas is the 4th in prevalence in Argentina, with a median survival of 4?6 months. Type I Interferons (IFNs) have important antitumor properties, but the precise mechanisms by which IFNs generate antineoplastic responses remain incompletely defined.The aim of this study was to investigate the response of MIAPaCa-2 cell line to IFN-I and analyzed the modulation of autophagy and the capability to induce cell death.MIAPaCa-2 cells were treated with 1000 IU/ml of IFNα2b or IFNβ for 24h. IFNα2b triggered the accumulation of acidic vesicular, evaluated by AO dye and autolysosomes, observed by MDC stain. By contrast, IFNβ decreased the accumulation of these vesicles. Moreover, IFNα2b increased the number and the size of LC3-positive vesicles respect to untreated cells meanwhile IFNβ decreased the number of autophagosomes per cell in RFP-LC3 transfected cells. Similar results were obtained by western blot. In addition, both IFNs inhibited MIAPaCa-2 cell growth assessed by [3H]-thymidine incorporation. IFNα2b inhibited cell growth in a 28.3±4.7 % and 43.3±1.5 % for 24 and 48 h, respectively (p0.0001). These results demonstrated that IFNα protected MIAPACa-2 cells to the pro-apoptotic effect of gemcitabine by induction of autophagy mean while IFNβ facilitated it, inhibiting autophagy process