Experimental study on lung cancer-targeted oncostatin M gene therapy induced by ionizing radiation

Abstract

To improve the efficacy and selectivity of gene therapy for lung cancer through inducing oncostatin M (OSM) gene expression by radiation via the early growth response gene-1 (Egr-1) promoter. The radio-inducible OSM gene was constructed by insertion of Egr-1 promoter into upstream of the OSM gene. The expression of OSM in lung adenocarcinoma cell line A549 which was transfected with pEO and exposed to different doses of γ-ray irradiation was analyzed, and the relative survival fraction of cells and cell survival curve were observed. To examine the efficacy of this pEO gene therapy in vivo, the tumor supression effects were investigated in 40 nude mice bearing lung tumors. Expression of OSM gene in A549 cells transfected with pEO plasmids was markedly upregulated in a radiation dose-dependent manner. A gene therapy experiment in vitro showed that pEO transfected A549 cells became highly sensitive to ionizing radiation. pEO transfected tumors regressed significantly after a combination therapy with irradiation in all mice (n=10), and three tumors disappeared in 3 weeks without any side effect. The results indicate that tumor targeted expression of OSM gene under the control of a radio-inducible promoter represents a novel strategy for safe and effective gene therapy for lung cancer and might be widely applied in the future.