Zhou B, Zhang D, Pei S M, Zhang H, Du H C, Jin Y P, Lin D G
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Pol J Vet Sci. 2017 Mar 28;20(1):103-110. doi: 10.1515/pjvs-2017-0014.
Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line. As compared it to its parental cell line (CMT7364), CMT7364/5-FU showed different morphology, cross-resistant to other chemo-drugs and a prolonged population doubling time (PDT). The drug efflux pump proteins (ABCB1 and ABCG2) in CMT7364/5-FU were up-regulated. In vivo, the similar result revealed that CMT7364/5-FU cell line was more resistant to 5-FU. In conclusion, a 5-FU-resistant canine mammary tumor cell line (CMT7364/5-FU) was successfully established, it can serve as a good model for researching the mechanism of MDR and screening effective agents to reverse drug resistance.
犬乳腺肿瘤是未绝育母犬中最常见的肿瘤。手术并非总能解决问题，对于这些患者建议进行化疗。然而，由于多药耐药性（MDR），化疗可能总会失败。通过逐步提高培养基中5-氟尿嘧啶（5-FU）的浓度，建立了一株耐5-FU的犬乳腺肿瘤细胞系CMT7364/5-FU，以揭示耐药的分子机制。比较了亲代细胞系和耐药细胞系之间的细胞形态、对药物的敏感性、生长曲线、蛋白质表达以及体内化疗敏感性。与亲代细胞系（CMT7364）相比，CMT7364/5-FU表现出不同的形态，对其他化疗药物具有交叉耐药性，且群体倍增时间（PDT）延长。CMT7364/5-FU中的药物外排泵蛋白（ABCB1和ABCG2）上调。在体内，类似的结果表明CMT7364/5-FU细胞系对5-FU更具抗性。总之，成功建立了一株耐5-FU的犬乳腺肿瘤细胞系（CMT7364/5-FU），它可作为研究多药耐药机制和筛选逆转耐药有效药物的良好模型。
