McMahon Melanie B, Bear Misty D, Kulp Samuel K, Pennell Michael L, London Cheryl A
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH 43210, USA.
Am J Vet Res. 2010 Jul;71(7):799-808. doi: 10.2460/ajvr.71.7.799.
To evaluate in vitro biological activity of gemcitabine, alone and in combination with Pamidronate or carboplatin, against canine osteosarcoma (OSA) cell lines.
In vitro cultures of OSA cell lines OSA8, OSA16, OSA32, and OSA36.
Cell lines were treated with gemcitabine alone or in combination with pamidronate or carboplatin. Cell viability was assessed with the water soluble tetrazolium-1 (WST-1) assay, cell cycle distribution was evaluated by means of propidium iodide staining, and apoptosis was assessed by measuring caspase-3/7 activity. Synergy was quantified by use of combination index (CI) analysis.
For all of the cell lines, treatment with gemcitabine induced growth inhibition, cell cycle arrest, and apoptosis. No synergistic or additive activity was identified when OSA cell lines were treated with gemcitabine in combination with pamidronate. However, when OSA cell lines were treated with gemcitabine in combination with carboplatin, a significant decrease in cell viability was observed, compared with treatment with carboplatin alone, and the drug combination was determined to be synergistic on the basis of results of CI analysis. For 3 of the 4 cell lines, this activity was greater when cells were treated with carboplatin prior to gemcitabine rather than with gemcitabine prior to carboplatin.
Gemcitabine exhibited biological activity against canine OSA cell lines in vitro, and a combination of gemcitabine and carboplatin exhibited synergistic activity at biologically relevant concentrations. Findings support future clinical trials of gemcitabine alone or in combination with carboplatin for the treatment of dogs with OSA.
评估吉西他滨单独使用以及与帕米膦酸盐或卡铂联合使用时，对犬骨肉瘤（OSA）细胞系的体外生物学活性。
OSA细胞系OSA8、OSA16、OSA32和OSA36的体外培养物。
细胞系分别用吉西他滨单独处理，或与帕米膦酸盐或卡铂联合处理。通过水溶性四氮唑盐-1（WST-1）检测评估细胞活力，用碘化丙啶染色评估细胞周期分布，并通过测量半胱天冬酶-3/7活性评估细胞凋亡。使用联合指数（CI）分析对协同作用进行量化。
对于所有细胞系，吉西他滨处理均诱导生长抑制、细胞周期停滞和细胞凋亡。当OSA细胞系用吉西他滨与帕米膦酸盐联合处理时，未发现协同或相加活性。然而，当OSA细胞系用吉西他滨与卡铂联合处理时，与单独使用卡铂处理相比，观察到细胞活力显著降低，并且根据CI分析结果确定该药物组合具有协同作用。对于4个细胞系中的3个，当细胞先用卡铂处理再用吉西他滨处理时，这种活性比先用吉西他滨处理再用卡铂处理时更强。
吉西他滨在体外对犬OSA细胞系表现出生物学活性，并且吉西他滨与卡铂的组合在生物学相关浓度下表现出协同活性。这些发现支持未来对吉西他滨单独或与卡铂联合用于治疗犬OSA的临床试验。
