长春新碱诱导建立人结肠癌MDR动物模型及MDR1和MRP1基因表达
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Establishment of a mouse model of MDR colon carcinoma induced by vincristine and expression of MDR1 and MRP1 genes
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    摘要:

    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Western 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。

    Abstract:

    ObjectiveTo established a mouse model of multi-drug resistant (MDR) colon carcinoma and initially explore the mechanism of drug resistance.MethodsThe 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.ResultsThe 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. ConclusionsA 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. 

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李长龙,柯贤福,郭红刚,卢领群,戴方伟,萨晓婴.长春新碱诱导建立人结肠癌MDR动物模型及MDR1和MRP1基因表达[J].中国实验动物学报,2012,(4):56~61.

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