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

• Published in: Cell biology international 2007-05, Vol.31 (5), p.500-507
• Main Authors: Dong, Ai-Qiang, Kong, Min-Jian, Ma, Zhi-Yuan, Qian, Jian-Fang, Xu, Xiao-Hong
• Format: Article
• Language: English
• Subjects: Animals; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Division - genetics; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Lung cancer; Mice; Mice, Nude; Receptor, IGF Type 1 - genetics; RNA interference; RNA, Small Interfering - genetics; Transplantation, Heterologous; Type I insulin-like growth factor receptor
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1016/j.cellbi.2006.11.017

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.