中文摘要：

目的利用L型和D型氨甲喋呤（MTX）对映体分别建立人肺腺癌A549细胞株裸鼠耐药模型，为进一步揭示MTX对映体体内活性差异的原因提供实验平台。方法裸鼠皮下分别接种A549、耐药细胞株A549/L-MTX、A549/D-MTX各6×10^6个/0.2ml，观察肿瘤生长特性；瘤体原代培养后四甲基偶氮唑兰（MTT）法检测耐药指数（resistance index RI）；免疫组化（IHC）检测ki-67、多药耐药相关蛋白1（multidrug resistance-associated protein1，MRP1）、survivin变化。结果从肿瘤生长曲线上看瘤体积三者差异有统计学意义（P〈0.05），A549/L-MTX/nude组体积更小。A549/L-MTX/nude移植瘤RI为4.9，为低度耐药，A549/D-MTX/nude移植瘤RI为14.5，为中度耐药。A549/L-MTX/nude相关蛋白总体表达低于A549/D-MTX/nude，两者表达差异有统计学意义（P均〈0.05）。结论成功建立对MTX两种对映体耐药的A549细胞株裸鼠肿瘤模型，且两种耐药细胞具有不同耐药特性，为研究MTX对映体体内抗肿瘤活性差异提供了较好的实验平台。

英文摘要：

Objective To establish a nude mice xenograft model of MTX enantiomers-resistant human lung carcinoma A549 for exploring the mechanism of tumor proliferation and drug-resistance. Methods A549 and two drug-resistant cell lines ,A549/L-MTX and A549/D-MTX were transplanted into nude mice subcutaneously in right flank. Tumor growth activities and xenografts＇ resistance index were compared. The expression of proliferation marker ki-67, multi-drug resistance-associated protein 1 （MRP1） and apoptosis inhibitor survivin were assessed by immunohistochemistry. Results Tumor volume of A549/L-MTX/nude grew smaller than that of A549/D-MTX/nude, and the tumor ki-67, MRP1 and survivin expression of A549/L-MTX/nude decreased （P〈0.05）. Low drug-resistance （RI=4.9） in A549/L-MTX/nude tumor and medium drug-resistance （RI = 14. 5） in A549/D-MTX/nude tumor were shown. Conclusions Nude mice xenografts of MTX enantiomers-resistant A549 cells were established and retained the characteristics of tumor drug-resistance. This provides an ideal animal model for future study of MTX enantiomers.