Antitumor and radiosensitization effect of ~(12)C~(6+) heavy-ion irradiation mediated by radiation-i

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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~12C~(6+)tion 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~12C~(6+)tion 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. Theresults also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with~12C~(6+)tion 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. Radio genetic therapy which combines genes therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirus based 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 ~ 12C ~ 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 ~ 12C ~ (6+) tion 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 The results also demonstrate that use of an oncolytic adenovirus based radiation-inducible gene therapy system together with ~ 12C ~ (6 +) tion therapy due to 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.
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