Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, Northeastern University , Boston, Massachussets, United States.
ACS Chem Biol. 2013 Dec 20;8(12):2771-7. doi: 10.1021/cb4007024. Epub 2013 Oct 17.
Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of severe Gram-negative and Gram-positive bacterial infections. While bactericidal effects of aminoglycosides are due to binding to the 30S subunit of the bacterial ribosome, aminoglycosides can affect protein synthesis, intracellular calcium levels, and levels of reactive oxygen species (ROS) in eukaryotic cells. While aminoglycosides can be cytotoxic at high concentrations, our results show that at much lower doses, gentamicin can be implemented as a sensitizing agent for the NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin, and vinblastine in vitro. We have also established that this sensitization is reliant on the ROS response generated by gentamicin.
氨基糖苷类抗生素是一种广谱抗生素，用于治疗严重的革兰氏阴性和革兰氏阳性细菌感染。虽然氨基糖苷类抗生素的杀菌作用是由于与细菌核糖体的 30S 亚基结合，但它们也可以影响真核细胞中的蛋白质合成、细胞内钙离子水平和活性氧（ROS）水平。虽然高浓度的氨基糖苷类抗生素可能具有细胞毒性，但我们的研究结果表明，在低得多的剂量下，庆大霉素可以作为非小细胞肺癌细胞系 NCI-H460 的增敏剂，提高体外喜树碱、地高辛和长春碱的疗效。我们还确定这种增敏作用依赖于庆大霉素产生的 ROS 反应。
