耐多柔比星S180荷瘤小鼠模型的建立

Establishment of S180 Mouse Model of Multidrug Resistance Induced by Repeatedly Low-Dose Doxorubicin

目的采用低剂量多柔比星诱导,建立耐多柔比星的S180的荷瘤小鼠模型。方法建立腹水型S180荷瘤小鼠模型。对荷瘤小鼠反复低剂量应用多柔比星,逐步诱导产生耐多柔比星的S180荷瘤小鼠模型。并通过多柔比星对S180杀伤率、流式细胞术动态检测MDR表达情况等评价模型建立情况。结果实验组小鼠自用药后1周MDR表达逐渐增高,自第5周后显著性增加(P<0.05),第7周的P-gp表达率是第1周的近10倍。第5周时实验组MDR阳性表达小鼠占66.7%,第7周占77.8%。多柔比星对S180杀伤率逐月降低。经传代后腹水型小鼠S180细胞的表达稳定。结论本方法简单方便,可用于在体肿瘤多药耐药研究。

OBJECTIVE To establish the mouse model with multidrug resistance（MDR） induced by repeatedly low-dose doxorubicin.METHODS The mice inoculated by S180 cells were injected with doxorubicin in low dosage.The expression of MDR gene was assayed by flow cytometry and cellular-killed rate was also determined.RESULTS It was found that,in the experiment group,the expression of MDR gene gradually increased after one week of doxorubicin and markedly increased since 5th week of treatment.At 5th week,the percentage of mice with positive MDR gene expression was 66.7% and it was 77.8% at 7th week.And the expression was stable in the cell line.Cellular-killed rate was gradually decreased along with the progress of repeated doxorubicin.CONCLUSION The method is simple and can be used in vivo MDR study.