Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
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DOI：
10.1038/10533
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发表时间：
1999-07-01
期刊：
影响因子：
82.9
通讯作者：
Saltiel, AR
中科院分区：
文献类型：
--
作者：
Sebolt-Leopold, JS;Dudley, DT;Saltiel, AR
丝裂原活化蛋白激酶途径被认为是细胞生长和分化所必需的。在这里，我们报告发现了一种高效和选择性的上游激酶MEK抑制剂，是口服活性。用这种抑制剂治疗后，小鼠和人结肠癌小鼠的肿瘤生长抑制高达80%。在广泛的剂量范围内实现了疗效，没有毒性迹象，并且与切除肿瘤中活化的丝裂原活化蛋白激酶水平的降低相关。这些数据表明，MEK抑制剂代表了一个有前途的，非细胞毒性的方法，结肠癌的临床管理。
The mitogen-activated protein kinase pathway is thought to be essential in cellular growth and differentiation. Here we report the discovery of a highly potent and selective inhibitor of the upstream kinase MEK that is orally active. Tumor growth was inhibited as much as 80% in mice with colon carcinomas of both mouse and human origin after treatment with this inhibitor. Efficacy was achieved with a wide range of doses with no signs of toxicity, and correlated with a reduction in the levels of activated mitogen-activated protein kinase in excised tumors. These data indicate that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer.