Autophagy prevents apoptotic death in pancreatic tumor

PAPADEMETRIO D; CAVALIERE V; SIMUNOVICH T; COSTANTINO S.; LOMBARDO T; COLOMBO M; BLANCO G; FADER KAISER C; ALVAREZ E.

Whistle

Simposio; Keystone Sympòsia on Molecular and Cellular Biologý; 2011

Keystone

Pancreatic cancer is an aggressive disease whose incidence has risen in the last two decades, being presently the fourth cause of cancer death in the western world. Currently, gemcitabine (20-20-difluorodeoxycytidine) represents the standard chemotherapy in all stages of pancreatic adenocarcinoma. However, survival benefit and clinical impact remains modest due to a high degree of intrinsic and acquired resistance. In several tumors, the lack of apoptosis could be related to the instauration of an autophagy process. The aim of this study was to verify if the blockage of autophagy process sensitized the cells to death by apoptosis by Gemcitabine. For that, we analyzed the capability of Gemcitabine (10-1000mg/ml) to induce apoptosis alone or after pre-treatment with 3-metyladenine (3-MA) 10mM on MIAPaCa-2 cell line, using the Annexin V-FITC/PI assay. In all cases Gemcitabine increased in a 30% the number of annexin + cells when the autophagy process was inhibited (52.6%) vs. the effect of Gemcitabine alone (22.0%) (p