sensitization of radio-resistant lung cancer cells with a b subunit of bacterial cytolethal distending toxin from aggregatibacter actinomycetemcomitans

Background: combination cancer therapy is a promising strategy whichemploys multiple therapeutic agents with different mechanisms of action along with minimal intolerable side effects. for example, a combination of radiotherapy with gene therapy can overcome the development of resistance to therapeutic doses of irradiation (ir) and normal tissue damages caused by high-dose radiation. recent studies have revealed radio-resistance in non-small cell lung cancer (nsclc) cells. in this study, for the first time, subunit b of cytolethal distending toxin (cdtb)-expressing plasmid was introduced as a sensitizer of the cells to ir with a high efficacy. methods: a vector expressing cdtb suicide gene of human periodontal bacterium aggregatibacter actinomycetemcomitans was constructed and then transfected into a549 cell line. in the next step, cells transfected with pcdna3.1/cdtb were irradiated and its growth inhibitory effect was evaluated in nsclc cancer in vitro bymtt (3-(4, 5-methylthiazol-2-yl) -2, 5-diphenyl-tetrazolium bromide) assay. terminal deoxyribonucleotidyl transferase-mediated dutp nick end labeling (tunel) assay were carried out in order to examine the apoptosis induction by a combination of ir with cdtb. results: our data indicated significant cell death in nsclc cells in comparison with controls with an increase from 5% in response to ir up to 73.27% for combination of ir with cdtb. moreover, the result of tunel assay showed significant differences in the number of apoptotic cells among the different affected groups. conclusions: our results confirmed that cdtb-expressing plasmid sensitizes nsclc cells to ir and significantly increases the efficacy of radiotherapy and therefore, combining toxin with ir has a synergistic effect on nsclc.