Rodriguez-Vicente J, Vicente-Ortega V
Department of Pathology, Faculty of Medicine, Campus de Espinardo, University of Murcia, Spain.
Pigment Cell Res. 1996 Dec;9(6):317-25. doi: 10.1111/j.1600-0749.1996.tb00124.x.
Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.
黑色素瘤的化疗效果不佳,必须使用增敏化合物来加强疗效。我们认为壬二酸(AZA)可以调节黑色素瘤对抗肿瘤药物的耐药性。因此,我们试图比较单独使用抗肿瘤药物与先用AZA治疗再使用抗肿瘤药物的体外治疗效果。我们进行了MTT试验,以评估美法仑、洛莫司汀(CCNU)、福莫司汀和4-羟基茴香醚(4-HA)对三种黑色素瘤细胞系(B16F10、SK-MEL-28和SK-MEL-1)的细胞毒性,以及用AZA(1 mM)预处理的调节作用。AZA对这三种细胞系显示出剂量依赖性的抗肿瘤活性。美法仑是最具活性的药物,其次是CCNU、福莫司汀和4-HA。最敏感的细胞系是B16F10,最不敏感的是SK-meL-1。先用AZA处理B16F10可增强美法仑(2.5倍)、CCNU(10倍)和福莫司汀(14倍)的效果;而对于SK-MEL-28和SK-MEL-1,只有CCNU和福莫司汀的细胞毒性增加。4-HA对所有三种细胞系都产生了拮抗作用。我们得出结论,AZA可增强CCNU和福莫司汀的体外细胞毒性。