Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits growth of human lung cancer cell line A549 in vitro and in nude mice

Abstract Type I insulin‐like growth factor receptor (IGF‐IR), which is frequently overexpressed in a variety of human cancers including lung cancer, mediates cancer cell proliferation and tumor growth. In this study, we used a human U6 promoter‐driven DNA‐template approach to induce hairpin RNA (hpRNA)‐triggered RNAi to silence IGF‐IR gene expression in the human lung cancer cell line A549, and then evaluate its effects on apoptosis, apoptosis‐related gene expression, and the growth of tumor cells in vitro and in nude mice. IGF‐IR expression levels were found to markedly decrease in cells transfected with a plasmid expressing hairpin siRNA for IGF‐IR (by more than 78.9%). Down‐regulation of IGR‐IR concomitantly accompanied reduction of bcl‐2 as well as pERK and pAkt levels, activation of caspase‐3, apoptosis and growth inhibition of A549 cells in vitro . Direct intratumoral injections of plasmid DNA expressing hpRNA for IGF‐IR significantly regressed pre‐established tumors in nude mice. Our results support the therapeutic potential of RNAi as a method for gene therapy in treating lung cancer.