目的：探讨Snail在乳腺癌MCF-7细胞移植瘤对多柔比星耐药中的作用及其可能的机制。方法：构建Snail基因真核表达载体 pcDNA3.1-Snail，转染至MCF-7细胞，筛选稳定表达Snail的MCF-7/Snail细胞，以转染空质粒pcDNA3.1的MCF-7细胞（MCF-7/pcDNA）为对照。构建小鼠MCF-7/Snail及MCF-7/pcDNA细胞移植瘤模型，注射多柔比星，观测移植瘤生长，计算抑瘤率。免疫组织化学方法检测移植瘤组织中Snail、多药耐药基因-1（multidrug resistance-1, MDR-1）和基质金属蛋白酶-9（matrix metalloproteinase-9，MMP-9）的表达。结果：成功构建pcDNA3.1-Snail 表达载体，转染MCF-7细胞后获得MCF-7/Snail和MCF-7/pcDNA细胞，并制备小鼠移植瘤。多柔比星治疗后，MCF-7/Snail细胞移植瘤的瘤重明显高于MCF-7/pcDNA细胞移植瘤\[（1.413±0.674）g vs （1.257±0.576）g，P<0.05\]，多柔比星对MCF-7/Snail移植瘤抑瘤率明显低于MCF-7/pcDNA移植瘤（18.42% vs 30.18%，P<0.05），MCF-7/Snail细胞移植瘤的组织中Snail、MDR-1、MMP-9的表达均显著高于MCF-7/pcDNA移植瘤（408.08±20.39 vs 67.67±16.56，363.50±26.56 vs 55.08±12.23，396.25±16.03 vs 56.92±7.35；均P<001），且Snail与MDR-1和MMP-9的表达均呈正相关(r1=0.89，P<0.01; r2=0.81, P<0.01)。结论：Snail促进乳腺癌MCF-7细胞移植瘤对多柔比星的耐药，其机制与增强MDR-1和MM9-9表达有关。

Objective:To study the effect of Snail on resistance of breast cancer MCF-7 cell transplanted tumors to doxorubicin and its possible mechanism. Methods: Snail eukaryotic expression vector pcDNA3.1-Snail was constructed and transfected into MCF-7 cells, and MCF-7 cells with stable Snail expression (MCF-7/Snail cells) were screened. MCF-7 cells transfected with blank pcDNA3.1 (MCF-7/pcDNA cells) were used as control. MCF-7/Snail- and MCF-7/pcDNA-cell transplanted tumor models were established. After doxorubicin injection, the growth of transplanted tumors was observed, and the inhibitory rate of doxorubicin was calculated. The expressions of Snail, MDR-1 and MMP-9 in transplanted tumor tissues were examined by immunohistochemistry. Results: pcDNA3.1-Snail expression vector was successfully constructed, and MCF-7/Snail and MCF-7/pcDNA cells were obtained. After doxorubicin therapy, the transplanted tumor weight in MCF-7/Snail group was significantly higher than that in the MCF-7/pcDNA group (\[1.413±0674\]g vs \[1.257±0576\]g, P<0.05), and the inhibitory rate of doxorubicin was significantly lower (18.42% vs 30.18%, P<0.05). The expressions of Snail, MDR-1 and MMP-9 in transplanted tumor tissues were significantly higher than those in MCF-7/pcDNA group (408.08±20.39 vs 67.67±16.56, 363.50±26.56 vs 55.08±12.23, 396.25±16.03 vs 56.92±7.35, all P<0.05)，and the expression of Snail was positively correlated with that of MDR-1 and MMP-9 (r1=0.89, P<0.01; r2=0.81, P<0.01). Conclusion:Snail can increase resistance of breast cancer MCF-7 cell transplanted tumors to doxorubicin, which might be related with the increased expressions of MDR-1 and MMP-9 in breast cancer MCF-7 transplanted tumors.

山东省高等学校科技计划项目资助(No.J10LF64)