SURVIVIN: A LINK BETWEEN AUTOPHAGY AND SENESCENCE

MIHALEZ C.Y.; DEL VALLE RAMIREZ R.; LOMPARDÍA S. L.; PAPADEMETRIO D. L.; ALVAREZ E. M. C.

Congreso; Reunión Científica Anual Conjunta de SAIC, SAFE, SAB y SAP; 2019

Pancreatic cancer is highly resistant to chemotherapy. Gemcitabine (Gem) raises the levels of survivin expression accompanied by increases in autophagy levels. It has been described a link between autophagy and senescence. Hence, we proposed to evaluate if survivin would be mediating these processes in our cell lines and whether the SASPs produced by senescent cells could have an impact on the surrounding cells. Accordingly, we treated MIAPaCa-2 wt and KDSurv cells with Gem (10, 100 and 1000 μg/ml) alone or in combination with 3MA for 48 h and evaluated senescence by SA-β-Gal assay. Then, we determined apoptosis induction by Gem alone or in combination with 3MA by tunel assay. Besides that, we study the effect of SASPs on cell death and senescence. Supernatant of the cells treated with Gem were collected and added on fresh cells. We could determine in both lines that Gem increases the levels of senescence in a dose-dependent manner reaching values of 30% in the wt line and 60% in the KDSurv line (p 0.05), while in the KDSurv line, inhibition of autophagy sensitizing cells to the pro-apoptotic action of Gem (p