Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability.
Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability.
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DOI：
10.2302/kjm.59.10
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Muraki T
中科院分区：
文献类型：
--
作者：
Nozaki M;Yoshikawa M;Ishitani K;Kobayashi H;Houkin K;Imai K;Ito Y;Muraki T
我们探讨了半胱氨酰白三烯受体拮抗剂，普仑司特和孟鲁司特，阻止肿瘤细胞通过大脑和外周毛细血管迁移的可能性。为了研究肿瘤细胞通过脑毛细血管的迁移，将雄性Fisher大鼠在戊巴比妥麻醉下经小脑延髓池插管。在蛛网膜下腔给予花生四烯酸后，静脉内给予荧光标记PKH 67标记的RCN 9细胞，每30分钟收集一次中枢神经系统的样本，共8小时。花生四烯酸增加了液体体积，白色血细胞和RCN 9细胞计数升高。当在花生四烯酸给药前2小时给予时，普仑司特（而非孟鲁司特）减少了液体体积并抑制了白色血细胞和RCN 9细胞通过脑毛细血管外渗。此外，使用小鼠中的刘易斯肺癌转移模型来研究普仑司特和孟鲁司特对癌细胞通过一般毛细血管外渗的抑制作用。当小鼠被给予含有普仑司特或孟鲁司特的食物时，在爪切断后立即，两种药物都阻止了肿瘤转移，并且它们的存活时间延长。这些结果表明，普仑司特可抑制肿瘤细胞通过脑和外周毛细血管的迁移，而孟鲁司特仅抑制肿瘤细胞在外周毛细血管中的迁移。
We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlukast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.