Antitumor and radiosensitization effect of 12C6+ heavy-ion irradiation mediated by radiation-inducible gene therapy

Abstract

Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was constructed to improve the cancer curative effect. This gene therapy system incorporated the radiation-inducible early growth response gene (Egr-1) promoter and the anticancer gene tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To confirm the antitumor effect of Ad-ET combined with 12 C 6þ ion irradiation, the survival and apoptosis fraction of tumor cells HT1080 and normal cells MRC-5 in combination treatment were detected by CCK-8 assay and FACS analysis. Then the expression levels of TRAIL gene and protein were tested by real-time PCR and western blotting. The results show that 12 C 6þ ion irradiation could induce cell growth inhibition and apoptosis by activating the TRAIL gene expression in tumor cells, while exhibiting no obvious toxicity to the normal lung cell line MRC-5. The results also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with 12 C 6þ ion irradiation could cause synergistic antitumor effect specifically in tumor cells but not in normal cells. The results indicate that the novel radio genetic therapy could potentiate radiation treatment by improving the safety and efficiency of monotherapy, and provide theoretical support for clinical application of combination treatment.