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目的 建立一种人多药抗药性 (MDR)细胞株的裸鼠移植瘤模型并探讨其MDR特性 ,为筛选MDR逆转剂进行体内逆转MDR的研究提供模型。方法 按SPF级动物常规饲养裸鼠 ,鼠腋窝皮下接种 1× 10 7个细胞 ,观察成瘤率及生长特性 ,并比较裸鼠体内细胞与原代细胞耐药特性。细胞毒测定采用MTT法。P糖蛋白 (Pgp)的测定采用流式细胞仪法。结果 KBv2 0 0裸鼠移植瘤的成瘤率为 10 0 % ;在本研究的饲养条件下 ,19d瘤重可达 1 0～ 2 5 g ,平均 (2 1±0 4) g。原代及裸鼠体内KBv2 0 0对长春新碱 (VCR)的IC50分别为 1 479和 1 472 μmol·L-1,两者比较差异无显著性(P >0 0 5 )。原代及裸鼠体内KBv2 0 0的Pgp的表达率分别为 92 1%、91 9% ,二者差异无显著性 ;二者荧光强度亦未见明显改变 ,即Pgp表达量未见改变。 结论 以KBv2 0 0细胞所建立的裸鼠移植瘤模型 ,成瘤率高 ,在实验期间 15～ 2 0d内仍保持其MDR的特性 ,可提供做为MDR研究的体内模型。
Objective To establish a human multidrug-resistant (MDR) cell line xenograft model in nude mice and to investigate its MDR characteristics, providing a model for screening MDR reversal agents for in vivo reversal of MDR. METHODS: Normal animals were bred in SPF grade and nude mice were subcutaneously inoculated with 1×10 7 cells. The rate of tumor formation and growth characteristics were observed. The drug resistance characteristics of the cells in primary and nude mice were compared. The cytotoxicity assay uses the MTT method. P-glycoprotein (Pgp) was measured by flow cytometry. Results The tumorigenesis rate of transplanted tumors in KBv200 mice was 100%. In this study, the tumor weight of 19d could reach 10 to 25 g with an average of (2 1±0 4) g. The IC50 values of KBv200 against vincristine (VCR) in primary and nude mice were 1 479 and 1 472 μmol·L-1, respectively, and there was no significant difference between the two (P > 0.05). The expression rates of Pvp in KBv2 0 0 in primary and nude mice were 92 1% and 91 9%, respectively. There was no significant difference between the two groups. There was no significant change in the fluorescence intensity of KBv2 0, ie, the expression of Pgp did not change. Conclusion The xenograft tumor model established by KBv200 cells has a high tumorigenesis rate and maintains its MDR characteristics within 15 to 20 days during the experimental period. It can be used as an in vivo model for MDR studies.