Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.
Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.
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DOI：
10.1111/vco.12250
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发表时间：
2017-09
影响因子：
2.1
通讯作者：
Rebhun RB
中科院分区：
文献类型：
--
作者：
York D;Withers SS;Watson KD;Seo KW;Rebhun RB
辅助化疗可以提高局部控制无骨肉瘤的狗的生存时间，但大多数狗最终死于转移性疾病。氟喹诺酮类抗生素恩诺沙星已被证明可以抑制犬骨肉瘤细胞的存活和增殖。其他人已经报道氟喹诺酮类药物可以调节细胞对DNA损伤剂的反应，并且这些作用可能由p53活性差异介导。因此，我们确定了p53的状态和活性在三个犬骨肉瘤细胞系，并检查恩诺沙星单独使用或与阿霉素或卡铂化疗联合使用时的影响。Moresco和Abrams犬骨肉瘤细胞系含有p53突变，而在D17细胞或正常犬成骨细胞系中未发现突变。恩诺沙星添加到阿霉素或卡铂导致骨肉瘤细胞活力进一步降低;无论p53突变状态或下游活性如何，这种效果都是明显的。
Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity.