Zhu Yuyi, Weldon John E
Department of Biological Sciences, The Jess and Mildred Fisher College of Science and Mathematics, Towson University, Towson, MD, 21252, USA.
BMC Res Notes. 2019 May 27;12(1):293. doi: 10.1186/s13104-019-4337-6.
Recombinant immunotoxins (RITs) are antibody-toxin fusion proteins that can selectively eliminate populations of cells expressing specific surface receptors. They are in evaluation as therapeutic agents for cancer. RITs based on Pseudomonas exotoxin A (PE) are in use clinically for the treatment of hairy cell leukemia, and under trial for the treatment of other cancers. In an effort to improve the efficacy of PE-based RITs, we evaluated the potential of combination therapy with several common antibiotics (tetracycline, chloramphenicol, streptomycin, linezolid, fusidic acid, and kanamycin) on human cell lines HEK293, OVCAR8, and CA46. Antibiotics were selected based on their potential to inhibit mitochondrial protein synthesis and disrupt energy metabolism in cancer cells.
Tetracycline, chloramphenicol, linezolid, and fusidic acid alone killed cultured human cells at high concentrations. At high but nontoxic concentrations of each antibiotic, only chloramphenicol treatment of the Burkitt's lymphoma cell line CA46 showed enhanced cytotoxicity when paired with an anti-transferrin receptor/PE RIT. This result, however, could not be replicated in additional Burkitt's lymphoma cell lines Ramos and Raji. Although the six antibiotics we tested are not promising candidates for RIT combination therapy, we suggest that fusidic acid could be considered independently as a potential cancer therapeutic.
重组免疫毒素（RITs）是抗体-毒素融合蛋白，可选择性清除表达特定表面受体的细胞群体。它们正作为癌症治疗药物进行评估。基于铜绿假单胞菌外毒素A（PE）的RITs已在临床上用于治疗毛细胞白血病，并正在进行治疗其他癌症的试验。为了提高基于PE的RITs的疗效，我们评估了几种常见抗生素（四环素、氯霉素、链霉素、利奈唑胺、夫西地酸和卡那霉素）与人类细胞系HEK293、OVCAR8和CA46联合治疗的潜力。选择抗生素是基于它们抑制癌细胞线粒体蛋白质合成和破坏能量代谢的潜力。
四环素、氯霉素、利奈唑胺和夫西地酸单独使用时在高浓度下可杀死培养的人类细胞。在每种抗生素的高但无毒浓度下，只有氯霉素处理伯基特淋巴瘤细胞系CA46与抗转铁蛋白受体/PE RIT联合使用时显示出增强的细胞毒性。然而，这一结果在另外的伯基特淋巴瘤细胞系Ramos和Raji中无法复制。尽管我们测试的六种抗生素不是RIT联合治疗的有前景的候选药物，但我们建议夫西地酸可独立被视为一种潜在的癌症治疗药物。
