Wu Rui, Ding Wanjing, Liu Tao, Zhu Hong, Hu Yongzhou, Yang Bo, He Qiaojun
Zhejiang University, Hangzhou, China.
Cancer Lett. 2009 Nov 18;285(1):13-22. doi: 10.1016/j.canlet.2009.04.042. Epub 2009 Aug 3.
The present data showed that a novel synthesized compound, N-acetyl-N-(4-(4-methoxyphenyl-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)acetamide (XN05), exhibited potent antitumor activity against various cancer cells in vitro. XN05-treatment in human hepatocellular carcinoma cells resulted in the accumulation of G2/M phase cells and finally induced apoptosis assessed by flow cytometry analysis. Western blot and immunofluorescence experiments indicated that XN05 depolymerized microtubules similar to the effect of combretastatin-A4. In addition, XN05-treatment influenced the expression of cell cycle and apoptosis related proteins in BEL-7402 cells, which was associated with the appearance of phosphorylated Bcl-2. Taken together, all the data demonstrated that XN05 exhibited its antitumor activity through disrupting the microtubule assembly, causing cell cycle arrest and consequently inducing apoptosis in BEL-7402 cells. Therefore, the novel compound XN05 is a promising microtubule inhibitor that has great potentials for therapeutic treatment of various malignancies.
目前的数据表明，一种新型合成化合物N-乙酰-N-(4-(4-甲氧基苯基-3-(3,4,5-三甲氧基苯基)异恶唑-5-基)乙酰胺(XN05)在体外对多种癌细胞表现出强大的抗肿瘤活性。用XN05处理人肝癌细胞导致G2/M期细胞积累，最终通过流式细胞术分析诱导细胞凋亡。蛋白质免疫印迹和免疫荧光实验表明，XN05使微管解聚，其作用类似于康普他汀A4。此外，用XN05处理影响了BEL-7402细胞中细胞周期和凋亡相关蛋白的表达，这与磷酸化Bcl-2的出现有关。综上所述，所有数据表明XN05通过破坏微管组装、导致细胞周期停滞并因此诱导BEL-7402细胞凋亡来发挥其抗肿瘤活性。因此，新型化合物XN05是一种有前景的微管抑制剂，在治疗各种恶性肿瘤方面具有巨大潜力。
