阿霉素诱导人乳腺癌细胞系耐药后的细胞行为变化

Behavior change of adriamycin resistant human breast cancer cell line MCF7

目的研究和完善乳腺癌细胞多药耐药机制及多药耐药后肿瘤细胞的性质、行为改变。方法分别对野生组(MCF-7)、阿霉素诱导的耐药组(MCF-7/ADM)、撤药60d组(MCF-7/撤药60d)进行细胞学分析,观察细胞增殖速度及群体增殖时间,SP免疫组化法检测细胞表型变化。结果MCF-7/ADM与MCF-7细胞增殖速度无明显差异,撤药组随着撤药时间的延长,细胞的增殖速度加快,群体倍增时间缩短;MCF-7/ADM、MCF-7/撤药60d细胞的分化程度低于MCF-7组;MCF-7/ADM的耐药相关标记蛋白Pgp、LRP、GST-π、HER-2表达较MCF-7明显增加,而雌激素受体(ER)、TOPO-Ⅱ转为阴性表达,孕激素受体(PR)随撤药时间的延长表达逐步减低。结论应用阿霉素诱导的MCF-7具有明显的耐药细胞性状,耐药细胞具有去分化的能力;耐药细胞的遗传和生化特性发生了变化,可用于肿瘤多药耐药机制的研究。

Objective To investigate mechanisms of resistance to adriamycin （ADR） by human breast cancer cell line MCF-7 and to find the alteration of features and celluar behavior of MCF-7 after exposure to ADR. Methods Proliferation speed, population doubling time of MCF （ wild type）, MCF-7/ADR （ exposure to adriamycin） and withdrawl group were respectively tested. Cell phenotype alteration was detected using SP immunohiatochemistry methods. Results No significant difference of proliferation speed was found between MCF-7/ADR and MCF cells. As exposure time prolonged, withdrawl group cells grew faster, thus population doubling time shortened. Differentiation of MCF-7/ADR and wthdrawl group was lower than wild group. The expression of drug resistance associated marker of MCF-7/ADR such as Pgp, LRP, GST-pi,TOPO Ⅱ was higher than that of MCF-7, ER turned to express negatively, and expression of PR gradually decreased as exposure continued. Conclusion MCF-7 cells exposed to ADR got drug resistant, their proliferation was not suppressed by withdrawl of ADR and even grew faster. Drug resistant cells gained dedifferentiation ability. Their heredity and biochemistry features changed, expression of target enzyme also altered and was reversible by drug withdrawl.