长春新碱诱导建立人结肠癌多药耐受性小鼠模型及MDR1和MRP1基因表达

目的建立人结肠癌多药耐受性动物模型并初步探索其耐药机制。方法结合体内外诱导方法建立人结肠癌多药耐受性动物模型,利用VCR和CTX的肿瘤抑制实验评价其MDR特性;利用real-time PCR和West-ern blotting等方法分析其P-gp/MDR1和MRP1基因和蛋白的表达。结果肿瘤抑制实验结果显示,MDR和敏感型结肠癌模型的肿瘤生长速度差异不显著,MDR结肠癌动物模型对于VCR和CTX的耐药性均有较大程度的提高;表达分析结果显示,人结肠癌MDR动物模型的P-gp/MDR1表达水平有较大提高,而MRP1表达没有显著变化。结论人结肠癌多药耐受性动物模型具有较好的多药耐受性,其多药耐受性表型主要是由于P-gp/MDR1过量表达所导致。

Establishment of a mouse model of MDR colon carcinoma induced by vincristine and expression of MDR1 and MRP1 genes

Objective To established a mouse model of multi-drug resistant（MDR） colon carcinoma and initially explore the mechanism of drug resistance.Methods The mouse models were generated by subcutaneous inoculation of drug-sensitive colon cancer HCT-8 cells and drug-resistant colon cancer HCT-8/VCR cells in mice.Their drug-resistance properties were assessed by vincristine（VCR） and cyclophosphamide（CTX） in vivo.The expression levels of multi-drug resistance gene 1（P-gp/MDR1） and multi-drug resistance-associated protein 1（MRP1） were detected by real-time PCR and Western blotting in tumor tissues of the mouse models.Results The speed of tumor growth was not significantly different between the MDR and sensitive mouse models.There was a more intense drug-resistance in the MDR mouse models than in the sensitive mouse models.Real-time PCR and Western blotting showed that the expression level of P-gp/MDR1 in the MDR mouse models was enhanced,but the MRP1 expression did not show significant differences.Conclusions A mouse model of MDR colon carcinoma has been successfully established.The mechanism of MDR in the mouse models is related to the overexpression of P-gp/MDR1 gene.