CAJ | 학술논문

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6×106个/0.2 ml,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.
목적 이용L형화D형안갑첩령(MTX)대영체분별건립인폐선암A549세포주라서내약모형,위진일보게시MTX대영체체내활성차이적원인제공실험평태.방법 라서피하분별접충A549、내약세포주A549/L-MTX、A549/D-MTX각6×106개/0.2 ml,관찰종류생장특성;류체원대배양후사갑기우담서란(MTT)법검측내약지수( resistance index RI);면역조화(IHC)검측ki-67、다약내약상관단백1(multidrug resistance-associated protein1,MRP1)、survivin변화.결과 종종류생장곡선상간류체적삼자차이유통계학의의(P<0.05),A549/L-MTX/nude조체적경소.A549/L-MTX/nude이식류RI위4.9,위저도내약,A549/D-MTX/nude이식류RI위14.5,위중도내약.A549/L-MTX/nude상관단백총체표체저우A549/D-MTX/nude,량자표체차이유통계학의의(P균<0.05).결론 성공건립대MTX량충대영체내약적A549세포주라서종류모형,차량충내약세포구유불동내약특성,위연구MTX대영체체내항종류활성차이제공료교호적실험평태.
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 resis-tance-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.