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Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma

机译:塞来昔布对人成视网膜细胞瘤细胞系和成视网膜细胞瘤小鼠模型的影响

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摘要

>Background/aim: Celecoxib, a cyclooxygenase-2 inhibitor and antiangiogenic agent, has demonstrated potent anticancer effects in preclinical studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, the authors investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease.>Methods: Growth inhibitory effects of celecoxib were evaluated in Y79 and Weri-RB1 human retinoblastoma cell lines by WST-1 cell proliferation assay. For animal study, two groups of 24, 8 week old LHβ-TAg transgenic mice were treated with celecoxib (250 mg/kg, orally once a day) or vehicle control, 5 days/week for 6 weeks. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumour burden was quantified by histopathological analysis.>Results: Celecoxib did not inhibit proliferation of Y79 or Weri-RB1 cells, even at concentrations far exceeding clinically achievable levels. No significant difference in ocular tumour burden between celecoxib treated and control mice (p = 0.73) was found.>Conclusion: Celecoxib was ineffective at inhibiting proliferation of retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumour growth in a murine model of this disease. On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma.
机译:>背景/目的:塞来昔布是一种环氧合酶2抑制剂和抗血管生成剂,已在临床前研究和人体临床试验中显示出有效的抗癌作用。为了评估该药物在治疗视网膜母细胞瘤中的潜在用途,作者研究了塞来昔布在视网膜母细胞瘤细胞系和该疾病的小鼠模型中的作用。>方法:评估了塞来昔布的生长抑制作用WST-1细胞增殖试验检测Y79和Weri-RB1人视网膜母细胞瘤细胞系中的表达。为了进行动物研究,将两组24只,8周大的LHβ-TAg转基因小鼠分别用塞来昔布(250 mg / kg,每天口服一次)或溶媒对照治疗,每周5天,共6周。在第43天处死小鼠。连续切除有核的眼睛,并通过组织病理学分析定量眼肿瘤的负担。>结果:塞来昔布不抑制Y79或Weri-RB1细胞的增殖,即使浓度远远超过临床水平可达到的水平。塞来昔布治疗组和对照组小鼠的眼肿瘤负荷无明显差异(p = 0.73)。>结论:塞来昔布在体外不能抑制视网膜母细胞瘤细胞增殖,在控制视网膜母细胞瘤肿瘤生长方面无效。这种疾病的小鼠模型。基于这些发现,口服塞来昔布疗法在视网膜母细胞瘤的治疗中不太可能具有临床效用。

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