小分子 CXCR2 和 CXCR1 拮抗剂抑制人结肠癌肝转移。

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.

Cancer Lett. 2011 Jan 28;300(2):180-8. doi: 10.1016/j.canlet.2010.10.004. Epub 2010 Oct 29.

CXCR1 and CXCR2 are G-protein coupled receptors, that have been shown to play important role in tumor growth and metastasis, and are prime targets for the development of novel therapeutics. Here, we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123, SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis. There were no differences in primary tumor growth. These studies demonstrate the important role of CXCR2/1 in colon cancer metastasis and that inhibition of CXCR2 and CXCR1, small molecule antagonists provides a novel therapeutic strategy.

CXCR1 和 CXCR2 是 G 蛋白偶联受体，已被证明在肿瘤生长和转移中发挥重要作用，是开发新型治疗药物的主要靶点。在这里，我们报告使用口服活性小分子拮抗剂（SCH-527123、SCH-479833）靶向 CXCR2 和 CXCR1 活性可抑制 CXCR2 和 CXCR1 活性，通过减少新生血管形成和增强恶性细胞凋亡来抑制人结肠癌肝转移。原发性肿瘤生长没有差异。这些研究表明 CXCR2/1 在结肠癌转移中的重要作用，抑制 CXCR2 和 CXCR1 的小分子拮抗剂提供了一种新的治疗策略。