伊立替康(Irinotecan)对SCA3细胞模型的影响  

The Effect of Irinotecan on SCA3 Cell Model

作　　者：王子见 陈添钰 张豆豆 何树妮 李繁 尤欢欢 WANG Zi-jian;CHEN Tian-yu;ZHANG Dou-dou;HE Shu-ni;LI Fan;YOU Huan-huan(School of Biological and environmental engineering,Xi’an University,Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling,Xi’an 710065,China;Institute of Human Medicine,Tuebingen University,Tuebingen 72076,Germany)

机构地区：[1]西安文理学院生物与环境工程学院,西安秦岭天然产物开发与创新药物研究重点实验室,西安710065 [2]德国图宾根大学人类医学研究所,德国图宾根72076

出　　处：《西安文理学院学报（自然科学版）》2023年第4期59-62,69,共5页Journal of Xi’an University(Natural Science Edition)

基　　金：陕西省大学生创新创业项目(S202111080043):“蒿甲醚通过激活p38信号通路调控ataxin-3核转运的分子机制研究”;陕西省大学生创新创业项目(S202111080031):“天麻素对SCA3细胞模型的影响”;陕西省大学生创新创业项目(6457):“蒿甲醚和天麻素联合用药对SCA3细胞模型的影响”;国家自然科学基金项目(82202067):“基于AKT/GSK3β信号通路探讨蒿甲醚调控ataxin-3入核在SCA3治疗中的作用机制”;西安市科技计划项目(2020KJWL04):“秦岭药用植物天麻的神经保护作用研究”;院长基金项目(YZJJ202104):“蒿甲醚通过HSP60信号通路调控ataxin-3聚集体发挥神经保护作用的机制研究”。

摘　　要：伊立替康(Irinotecan,CPT-11)是一种治疗癌症的化疗药物,主要代谢产物为7-乙基-10羟基喜树碱(7-Ethyl-10-hydroxycamptothecin,SN38).课题组实验筛选结果表明伊立替康对ataxin-3核质转运有潜在影响.通过免疫荧光、微孔过滤分析以及PretoBlue细胞活性检测等方法,探讨伊立替康对ataxin-3质核分离、突变ataxin-3形成的聚集体以及spinocerebellar ataxia type 3(SCA3)细胞活性的影响.结果表明伊立替康在10μM处理浓度时能够减少ataxin-3进入细胞核,但对蛋白聚集体没有影响;伊立替康在0.001μM或100μM处理浓度时,对SCA3细胞具有细胞毒性作用.本研究阐释了伊立替康对SCA3细胞模型的影响,揭示了旧药新靶点,为其他神经退行性疾病的致病机理和治疗药物研发提供新依据.Irinotecan(CPT-11)is a chemotherapeutic drug for cancer treatment.Its main metabolite is 7-Ethyl-10-hydroxycamptothecin(SN38).The preliminary results of the research group indicate that irinotecan has a potential impact on the nucleocytoplasmic transport of ataxin-3.In this paper,the effects of irinotecan on the cytoplasmic nuclear separation of ataxin-3,aggregates formed by mutant ataxin-3,and the activity of spinocerebella ataxia type 3(SCA3)cell models were investigated through immunofluorescence,filter trap analysis,and PretoBlue cell activity detection methods.The results showed that irinotecan reduced the entry of ataxin-3 into the nucleus at a concentration of 10μM,but had no effect on protein aggregates.Irinotecan exhibits cytotoxic effects on SCA3 cells at concentrations of 0.001μM or 100μM.This study explains the influence of irinotecan on SCA3 cell model,reveals new targets of old drugs,and provides new basis for pathogenesis of other neurodegenerative diseases and drug development.

关 键 词：伊立替康 SCA3 ATAXIN-3 细胞毒性 

分 类 号：R730[医药卫生—肿瘤]