Dual Expression of shAkt1 and Pdcd4 Suppresses Lung Tumorigenesis in K-ras(LA1) Mice

Abstract

Background/Aim: Lung cancer has the highest mortality rate among cancers and current therapies are not efficient. Therefore, novel therapeutic methods are urgently needed. Here, we examined the effectiveness of simultaneous Akt1 inhibition and Pdcd4 over-expression using a dual expression system in suppressing tumorigenesis in K-ras(LA1) mice (a lung cancer model). Materials and Methods: An shRNA targeting Akt1 (shAkt1) and cDNA of programmed cell death protein 4 (Pdcd4) were inserted into a dual expression vector (shAkt1+Pdcd4). A sorbitol diacrylate-polyethylenimine (SDA-PEI) carrier was used because of low toxicity and high transfection efficiency. Aerosolized SDAPEI/shAkt1+Pdcd4 complex was delivered to the mice twice a week for 4 weeks using a nose-only exposure inhalation chamber. Results: Simultaneous Akt1 inhibition and Pdcd4 over-expression synergistically induced potent antitumor effect. Analysis revealed significant reduction in lung tumor number. Conclusion: Dual expression of shAkt1 and Pdcd4 effectively suppresses lung tumorigenesis.