Combined knockdown of oncogenic RAS and Akt enhances cell death in MM.1S cells. Simultaneous depletion of oncogenic K-RAS and attenuation of Akt activity, either by shRNA-mediated knockdown (left) or by pharmacologic inhibition of Akt1 and 2 with Akti-1,2 (middle), significantly enhanced cell death in K-RAS mutated MM.1S cells. The concentrations chosen for the expression vectors for K-RAS shRNA (15 μg/mL) and Akt1 shRNA (10 μg/mL) and for Akti-1,2 (2.5μM) were such that an approximately medium size effect on the viability after 5 days in culture could be expected. RAS wild-type AMO-1 cells, which are insensitive to Akt inhibition, were not significantly affected by either single or combined knockdown of K-RAS and Akt1 (right).