Short hairpin RNA targeting AKT1 and PI3K/p85 suppresses the proliferation and self-renewal of lung cancer stem cells.

The aim of the present study was to investigate the effect of short hairpin (sh)RNA targeting AKT1 and phosphatidylinositol 3-kinase (PI3K)/p85 on the proliferation and self-renewal of lung cancer stem cells (LCSCs). The recombinant adenovirus expression vector, which contained shRNA targeting open reading frames of AKT1 and PI3K/p85, was transfected into LCSCs. It was found that AKT1 and PI3K/p85 expression was upregulated in LCSCs compared with that in the primary lung cancer cells. Recombinant adenovirus vector rAd5-siAKT1-siPI3K/p85 significantly downregulated AKT1 and PI3K/p85 mRNA and protein expression in LCSCs. The downstream factors, proliferating cell nuclear antigen (PCNA) and cyclin D1 were also downregulated, while p53 was upregulated. Following silencing of AKT1 and PI3K/p85, cell proliferation, tumor sphere formation and tumor formation in NOD/SCID mice were also reduced. According to the present results, it was hypothesized that the PI3K/Akt signaling pathway is important in the self-renewal and proliferation of LCSCs, and that targeting the PI3K/Akt signaling pathway decreases the rate of tumor formation in vivo. [ABSTRACT FROM AUTHOR]