放线菌B亚基细菌性细胞致死性畸变毒素对癌症耐药肺细胞的致敏作用

H. Yaghoobi, B. Kazemi, M. Bandehpour
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引用次数: 1

摘要

背景:癌症联合治疗是一种很有前途的策略,它采用多种具有不同作用机制的治疗剂,并将不可容忍的副作用降至最低。例如,将放射治疗与基因治疗相结合可以克服对治疗剂量的辐射(IR)产生的耐药性以及高剂量辐射引起的正常组织损伤。最近的研究揭示了非小细胞肺癌癌症(NSCLC)细胞的放射性耐药性。在本研究中,首次引入细胞致死性膨胀毒素(cdtB)表达质粒的B亚基作为细胞对IR的敏化剂。方法:构建人牙周放线综合聚集杆菌cdtB自杀基因载体,转染A549细胞。在下一步中,照射用pcDNA3.1/cdtB转染的细胞,并通过MTT(3-(4,5-甲基噻唑-2-基)-2,5-二苯基-四唑鎓溴化物)测定在体外评估其在NSCLC癌症中的生长抑制作用。进行末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)测定,以检测IR和cdtB联合诱导的细胞凋亡。结果:我们的数据表明,与对照组相比,NSCLC细胞的细胞死亡显著,从IR反应的5%增加到IR与cdtB联合作用的73.27%。此外,TUNEL测定结果显示,不同受影响组的凋亡细胞数量存在显著差异。结论:我们的研究结果证实,表达cdtB的质粒使NSCLC细胞对IR敏感,并显著提高放疗的疗效,因此,毒素与IR联合对NSCLC具有协同作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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, 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 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 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.
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