Sensitization of Radio-Resistant Lung Cancer Cells with a B Subunit of Bacterial Cytolethal Distending Toxin from <i>Aggregatibacter actinomycetemcomitans</i>
Journal Title: International Journal of Cancer Management - Year 2017, Vol 10, Issue 2
Abstract
Background Combination cancer therapy is a promising strategy which employs 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, <i>subunit B of cytolethal distending toxin (cdtB)</i>-expressing plasmid was introduced as a sensitizer of the cells to IR with a high efficacy. Methods A vector expressing <i>cdtB</i> suicide gene of human periodontal bacterium <i>Aggregatibacter actinomycetemcomitans </i>was constructed and then transfected into A549 cell line. In the next step, cells transfected with <i>pcDNA3.1/cdtB</i> were irradiated and its growth inhibitory effect was evaluated in NSCLC cancer in vitro by MTT (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 <i>cdtB</i>. 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 <i>cdtB</i>. 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 <i>cdtB</i>-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.
Authors and Affiliations
Hajar Yaghoobi, Bahram Kazemi, Mojgan Bandehpour
Keywords
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- EP ID EP237297
- DOI 10.5812/ijcp.5792
- Views 40
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