双硫仑抗癌作用研究进展

双硫仑作为一种治疗慢性酒精中毒的药物在临床中广泛使用。近几十年研究发现它除了戒酒作用还在治疗癌症中具有巨大潜力，针对它在体外和体内模型的研究结论已有部分在临床治疗中得到证实。双硫仑通过其代谢产物抑制乙醛脱氢酶活性导致体内乙醛含量积累，增加细胞毒性从而抑制肿瘤干细胞增殖分化；提高细胞内活性氧的浓度诱导细胞凋亡；抑制蛋白酶体活性，积累大量废弃蛋白质诱导细胞凋亡；通过抑制NF-κB下调来抑制上皮间质转化等。此外双硫仑与抗癌药物联合使用可提升抗癌药物药效。由于具有低毒、低成本且对肿瘤组织有趋向性等特点，双硫仑重新应用于临床作为抗癌药物具有广阔前景。简要回顾了双硫仑最新研究中阐明的双硫仑抗癌作用分子机制，展望了未来双硫仑用作新临床抗癌药物的前景，以期为双硫仑在抗癌药物中的应用研究提供参考。

Progress in Anticancer Effect of Disulfiram

Disulfiram is widely used in clinic as a drug for the treatment of chronic alcoholism.In recent decades,studies have found that it has great potential in the treatment of cancer in addition to its abstinence effect,and research conclusions on its in vitro and in vivo models have been partially confirmed in clinical treatment.Disulfiram inhibits the activity of acetaldehyde dehydrogenase through its metabolites,which leads to the accumulation of acetaldehyde content in vivo,increases cytotoxicity and thus inhibits the proliferation and differentiation of tumor stem cells;increases the concentration of intracellular reactive oxygen species to induce apoptosis;inhibits proteasome activity,accumulates a large number of waste proteins to induce apoptosis;inhibits the down-regulation of NF-kappa B to inhibit epithelial.In addition,the combination of disulfiram and anticancer drugs can improve the efficacy of anticancer drugs.Due to its low toxicity,low cost and tendency to tumor tissues,the reapplication of disulfiram in clinic as an anticancer drug has broad prospects.This article briefly reviewed the molecular mechanism of the anticancer effect of disulfiram as elucidated in the latest studies of disulfiram,and looked forward to the future prospects of disulfiram as a new clinical anticancer drug.The paper was expected to provide reference for the application research of disulfiram in anticancer drug.