Prolonged inhibition of tumoral progression by in vivo administration of RNA silencing for Akt1 and Trx system

HERRERA-PÁEZ J J, ALIPPE Y, PEREZ H, COLOMBO L, VANZULLI S, ANTICO-ARCIUCH VG, CARRERAS MC, PODEROSO JJ

Sao Pedro

Congreso; VII Meeting of the SFRBM South American Group. I Sao Paulo Advanced School on Redox Processes in Biomedicine; 2011

SFRBM South American Group

Akt1 is a Ser/Thr kinase involved in cell cycle progression, apoptosis, metabolism, tumorigenesis and tumor growth. Akt1 activity is redox-regulated, since subttle augments in oxidative state increases p-AKT1 levels in mitochondria and thus prevents its translocation to the nucleus. The general concept is that Akt1 prevents cell apoptotic activity, activates proliferation control pathways and controls cell growth, and that activity of Trx1 and 2 gives support to influences of the redox state on mitochondrial Akt phosphorylation. The aim was to inhibit LP07 tumoral growth by means of siRNA for Akt1 (siAkt1) and Trx1 and 2 (siTrx). Experiments were carried out on Balb/C mice of 60 days old, which were subcutaneously inoculated with LP07 lung tumoral cells. Tumors between 30 and 60 mm3 were transfected by electroporation with empty vector (EV), 25 µg of siAkt1 or 20 µg of siTrx1 and 2. Tumors transfected with siAkt showed the highest regression at 48 hours (0.38±0.04 vs 0.18±0.01 mm3 p