非小细胞肺癌紫杉醇耐药模型的建立

Establishment of model of paclitaxel resistant cell strain of non-small cell lung cancer

目的模拟肿瘤微环境缺氧的特征以及周剂量紫杉醇(PTX)用药规律,在缺氧条件下诱导非小细胞肺癌A549细胞系对PTX的耐药性,并分析MAPK激酶抑制剂PD98059对耐药性的影响。方法100μmol/LCoC l2诱导A549细胞7 d,待其适应缺氧环境后,采用12 nmol/L PTX诱导,每次16 h,每周1次,诱导3个月后分析A549对PTX的敏感性。采用PD98059与PTX共同处理耐药细胞,分析耐药细胞对PTX敏感性的变化。结果A549为PTX敏感细胞,IC50为1.25 nmol/L;缺氧条件下低浓度PTX诱导3个月后,IC50值增加为28.62 nmol/L,A549细胞对PTX耐受性明显增加。10μmol/L PD98059促进PTX对耐药细胞的抑制作用,两者具有联合效应。结论缺氧和低浓度PTX诱导可以导致A549细胞耐药性形成;而MAPK激酶抑制剂与PTX联合,可降低耐药性。

Objective According to the fact that most solid tumors grow under hypoxia condition of their tumor microenvironment and the feature of weekly paclitacxel treatment,paclitaxel-resistant cell strain of non-small cell lung cancer A549 was induced under hypoxia condition.Methods A549 cells were induced by 100 mol/L CoCl2 for one week,After they adapted to the hypoxia condition,these cells were treated with 12 nmol/L paclitaxol for 16 hours once a week.The sensitivity to paclitaxel of the parent A549 cells and p...