塞来昔布
血管生成
环氧合酶
癌症研究
新生血管
癌症
医学
结直肠癌
药理学
病理
索拉非尼
血管内皮生长因子
体内
细胞生长
生物
内科学
酶
生物化学
作者
Jaime L. Masferrer,Kathleen M. Leahy,Alane T. Koki,Ben S. Zweifel,Steven L. Settle,B M Woerner,D A Edwards,A G Flickinger,Ronald J. Moore,Karen Seibert
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2000-03-01
卷期号:60 (5): 1306-11
被引量:501
摘要
We provide evidence that cyclooxygenase (COX)-2-derived prostaglandins contribute to tumor growth by inducing newly formed blood vessels (neoangiogenesis) that sustain tumor cell viability and growth. COX-2 is expressed within human tumor neovasculature as well as in neoplastic cells present in human colon, breast, prostate, and lung cancer biopsy tissue. COX-1 is broadly distributed in normal, as well as in neoplastic, tissues. The contribution of COX-2 to human tumor growth was indicated by the ability of celecoxib, an agent that inhibits the COX-2 enzyme, to suppress growth of lung and colon tumors implanted into recipient mice. Mechanistically, celecoxib demonstrated a potent antiangiogenic activity. In a rat model of angiogenesis, we observe that corneal blood vessel formation is suppressed by celecoxib, but not by a COX-1 inhibitor. These and other data indicate that COX-2 and COX-2-derived prostaglandins may play a major role in development of cancer through numerous biochemical mechanisms, including stimulation of tumor cell growth and neovascularization. The ability of celecoxib to block angiogenesis and suppress tumor growth suggests a novel application of this anti-inflammatory drug in the treatment of human cancer.
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