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Antitumor mechanism of 3-bromopropionylamino benzoylurea on leukemia and lymphoma
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 7
- DOI:
- 10.3321/j.issn:0513-4870.2004.07.003
- Key Word:
- 3-溴代丙酰胺苯甲酰脲;抗肿瘤作用;细胞凋亡;Bcl-2磷酸化
Abstract： 目的研究新型微管微丝抑制剂3-溴代丙酰胺苯甲酰脲(JIMB01)抗人白血病和淋巴瘤的作用机制.方法细胞毒测定用MTT法、细胞周期分析用流式细胞仪检测、DNA片断产生用琼脂糖凝胶电泳法、细胞Bcl-2蛋白磷酸化用Western blot法等.结果JIMB01体外对所测定的9株人白血病和淋巴瘤细胞系均具有较强的抗增殖活性;可以使人白血病细胞(CEM)阻滞于有丝分裂期(G2/M期),并使细胞出现明显的凋亡形态变化和产生典型的DNA梯带;Western blot结果表明JIMB01处理的CEM细胞表达的Bcl-2蛋白发生磷酸化或高磷酸化;JIMB01可以激活CEM细胞caspase-3,8和9的催化活性,同时caspase-3抑制剂可以阻断JIMB01诱导CEM细胞凋亡.结论微管微丝抑制剂JIMB01抗肿瘤作用机制为阻滞肿瘤细胞于M期,并通过Bcl-2的蛋白磷酸化,继而经caspase通路诱导肿瘤细胞凋亡.
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