EXCESSIVE DOSE OF THE ANTI-APOPTOTIC FAMILY MEMBER SURVIVIN/BIRC5 INDUCES THE DEATH OF PANCREATIC CANCER CELLS

MAXIMILIANO A. DIAZ; MARIA NOÉ GARCIA; ASHLEY SIGAFOOS; DANIELA L. PAPADEMETRIO; ELIDA ALVAREZ; MARTIN FERNANDEZ-ZAPICO; DANIEL GRASSO

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a survival rate to 5 years of less than 5%. In this context, Survivin/BIRC5 is a protein belonging to the IAPs family of apoptotic inhibitors. In adult tissues, Survivin expression is almost exclusively found in tumors. Having in mind those data, efforts have been made to find the ways to decrease the levels of Survivin that goes in detriment of cancer cells viability, but no study was made about the overexpression of this protein. In this study, we analyze the effects of an incremented dose of Survivin in pancreatic cancer cells. We constructed an expression plasmid of Survivin (SurWT) and a mutant version where lysines 90 and 91 were replaced by arginine to avoid the degradative ubiquitination of Survivn (SurK90). Interestingly, a scratch assay revealed that stabilization of Survivin, by mean of stable transfection of SurK90 in the pancreatic cancer cell line Panc-1, significantly reduces migratory capacity of the cells. Furthermore, employing the “AlamarBlue” reagent, we observed a decrease in the viability of transiently transfected Panc-1 cells with SurK90 and after of 24h of SurWT. Additionally, the decreased viability becomes more pronounced with SurK90 in function of time (p