Humer Johannes, Ferko Boris, Waltenberger Andrea, Rapberger Ronald, Pehamberger Hubert, Muster Thomas
Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
Melanoma Res. 2008 Oct;18(5):314-21. doi: 10.1097/CMR.0b013e32830aaaa6.
Azidothymidine (AZT), currently used for HIV treatment, was also shown to induce cell growth inhibition and apoptosis in different human tumors. The objective of this study was to investigate the ability of AZT to inhibit the growth of human melanoma cells in vitro and in vivo. In cytotoxicity assays, treatment of cells with varying concentrations of AZT-induced inhibition of cell growth and apoptosis in three human melanoma cell lines without affecting the growth of nontumorigenic cells. AZT-dependent inhibition of proliferation was accompanied by a significant S-phase arrest of the cell cycle. Coexposure of cells to AZT during cisplatin treatment showed a synergistic effect on cytotoxicity. Moreover, AZT monotreatment of melanoma in a severe combined immunodeficiency-mouse xenotransplantation model resulted in significant tumor reduction. These results demonstrate for the first time the antimelanoma activity of AZT, suggesting its clinical utilization either as a sole agent or in combination with other chemotherapeutic agents.
叠氮胸苷（AZT）目前用于治疗艾滋病，研究还表明它能抑制不同人类肿瘤的细胞生长并诱导细胞凋亡。本研究的目的是调查AZT在体外和体内抑制人黑色素瘤细胞生长的能力。在细胞毒性试验中，用不同浓度的AZT处理细胞可抑制三种人黑色素瘤细胞系的细胞生长并诱导细胞凋亡，而不影响非致瘤细胞的生长。AZT依赖性增殖抑制伴随着细胞周期显著的S期阻滞。在顺铂治疗期间，细胞与AZT共同暴露显示出对细胞毒性的协同作用。此外，在严重联合免疫缺陷小鼠异种移植模型中，AZT单一治疗黑色素瘤可显著缩小肿瘤。这些结果首次证明了AZT的抗黑色素瘤活性，表明其可作为单一药物或与其他化疗药物联合用于临床。
