FTY720 and lung tumor development
FTY720 and lung tumor development
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DOI：
10.1016/j.intimp.2008.12.007
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发表时间：
2009-06-01
影响因子：
5.6
通讯作者：
Bueno, Valquiria
中科院分区：
文献类型：
--
作者：
Antunes Salinas, Natalia Regina;Fujiyama Oshima, Celina Tizuko;Bueno, Valquiria
FTY 720已被证明可以在实验模型中预防癌症的发展，但没有报道这种有益效果是否与给药时间点有关。通过尿烷注射随后不同时期施用FTY 720在小鼠中诱导肺腺瘤以评估肺肿瘤发展。BALB/c小鼠以1.5g/kg的两个剂量腹膜内接受氨基甲酸乙酯，并且在氨基甲酸乙酯注射后立即开始（G2 n = 5）、在氨基甲酸乙酯注射后4周（G3 n = 10）、在氨基甲酸乙酯注射后8周（G4 n = 10）和不施用FTY 720（G1 n = 5），接受FTY 720的五个每日剂量（lmg/kg/天）。乌拉坦给药后24周，评价小鼠血液中白细胞的数量，脾脏中淋巴细胞的数量，并评价肺组织学、PCNA和VEGF表达的变化。在尿烷注射后8周，未治疗组（G1; 0.0-7.0）和FTY 720治疗组（G4：0.0-6.0）的肺结节数量均较高。G4组乳头状结节数量最多。G1和G4组的脾细胞和中性粒细胞数量较低。在早期FTY 720处理的小鼠（G2）中，我们观察到PCNA染色的轻微降低以及VEGF强染色的较低百分比。因此，我们的数据表明FTY 720治疗的益处是时间依赖性的，并且当在肺肿瘤诱导后的早期施用时，该药物可能会损害癌症的发展。(C)2008 Elsevier B. V.保留所有权利。
FTY720 has been shown to prevent cancer development in experimental models but there is no report whether this beneficial effect is associated with the time point of the drug administration. Lung adenoma was induced in mice by urethane injection followed by different periods of FTY720 administration in order to evaluate lung tumor development. BALB/c mice received urethane intraperitoneally in two doses of 1.5 g/kg and were submitted to five daily doses of FTY720 (1 mg/kg/day) starting just after urethane injection (G2 n = 5), 4 weeks after urethane injection (G3 n = 10), 8 weeks after urethane injection (G4 n = 10) and no FTY720 administration (G1 n = 5). Twenty-four weeks after urethane administration mice were evaluated for the number of leukocyte in blood, lymphocytes in spleen, and lungs were evaluated for changes in histology, PCNA and VEGF expression. Lung nodules were present in higher numbers both in non treated (G1; 0.0-7.0) and FTY720 treated 8 weeks after urethane injection (G4: 0.0-6.0). G4 Group also presented the highest number of papillary nodules. G1 and G4 groups presented the lower number of splenocytes and neutrophils. In early time FTY720 treated mice (G2) we observed a slight decrease in PCNA staining and also the lower percentage of VEGF intense staining. Therefore, our data suggest that the benefits of FTY720 treatment are time-dependent and when administered in early periods after lung tumor induction this drug could impair cancer development. (C) 2008 Elsevier B.V. All rights reserved.