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.

GABABReceptor Activation Protects Neurons from Apoptosis via IGF-1 Receptor Transactivation

“…Whenever DMSO or alcohol were used, HBS containing the same concentration of DMSO and/or alcohol were used as the RNAi transfection in MEF cells and primary cerebellar granule neurons. For IGF-R RNAi knockdown experiment in MEF cells, mammalian shRNA constructs were designed as described previously (Dong et al, 2007). First, we design the target site of small hairpin RNAs (shRNA) for IGF-1R from 3476 to 3494 cDNA (NM_000875.2).…”

Inhibitory effect of siRNA targeting IGF-1R on endometrial carcinoma

“…RNA interference is widely used to explore gene function and used as a method of gene therapy for lung cancer [19], pancreatic cancer [20], colon cancer [21] and gastric cancer [22]. Although short hairpin RNA delivered by plasmid, retroviral vectors and adenoviral vectors has priority over chemically synthesized siRNA, there are many dis- Fig.…”

RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo

“…Tumor volume was determined based on the following formula: tumor volume 5 (major axis) 3 (minor axis) 2 3 1/2. 29 After a 30-day follow-up period, mice were euthanized and the tumors were removed. Harvested tumors were cut into 2 parts, 1 placed in liquid nitrogen and then frozen at 280°C and the other fixed by 4% paraformaldehyde and then embedded by paraffin.…”