吴茱萸碱部分通过人白介素1所介导的途径诱导人黑色素瘤A375-S2细胞死亡  

Evodiamine induced human melanoma A375-S2 cell death partially through interleukin 1 mediated pathway

作　　者：王澈[1] 王敏伟[1] 田代真一 小野寺敏 池岛乔[1] 

机构地区：[1]沈阳药科大学中日医学药学研究所 [2]昭和药科大学病态科学研究室

出　　处：《中国药理学通报》2005年第12期1478-1481,共4页Chinese Pharmacological Bulletin

摘　　要：目的研究吴茱萸碱(evodiamine)诱导人黑色素瘤A375S2细胞死亡的作用机制及其与细胞因子人白介素1(interleukin1,IL1)信号转导途径之间的关系。方法MTT检测法,DNA凝胶电泳法及Westernblot法。结果IL1受体拮抗因子(IL1receptorantagonist,IL1ra)在24h时能够部分抑制吴茱萸碱诱导的A375S2细胞死亡。吴茱萸碱在诱导A375S2细胞死亡的过程中,Fas配体(Fasligand,FasL)的蛋白表达量升高,激活其下游的caspase8和caspase3,进而引起DNA的损伤并激活p53蛋白,同时Bax/Bcl2的蛋白表达比例被上调。在经过IL1ra预处理后,这些变化均被部分的抑制或逆转。结论吴茱萸碱诱导A375S2细胞死亡的作用是部分通过IL1介导的信号转导途径而实现的。Aim To study the mechanism of evodiamine-induced A375-S2 cell death and the relationship of signal transduction pathways between evodiamine and IL-1. Methods MTT assay, agarose gel electrophoresis and Western blot analysis were carried out. Results IL-1 receptor antagonist （ IL-1 ra ） partially inhibited evodiamine-induced cell death in A375-S2 cells. In A375-S2 cell death, evodiamine increased the expression of Fas-ligand （Fas-L） and caused the cleavage of procaspas-8 and -3. Subsequently, evodiamine induced p53 activation, up-regulation of Bax/ Bcl-2 ratio and DNA degradation. Whereas pretreatment of IL-lra was capable of partially attenuating or reversing these changes induced by evodiamine. Conclusion Evodiamine induced human melanoma A375- S2 cell death partially through interleukin 1-mediated signal pathway.

关 键 词：吴茱萸碱 人白介素1 A375-S2细胞 FAS CASPASE p53 BAX/BCL-2 

分 类 号：R282.71[医药卫生—中药学] R287[医药卫生—中医学]