期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 30, 页码 11127-11132出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410432111
关键词
-
资金
- National Institute of Environmental Health Sciences [R01 ES02710]
- Superfund [P42 ES04699]
- National Institutes of Health/National Institute for Occupational Safety and Health [U54 OH07550]
- National Heart, Lung and Blood Institute [HHSN268201000043]
- Research Investments in the Sciences and Engineering Program of the University of California, Davis
- Stop and Shop Pediatric Brain Tumor Fund
- C. J. Buckley Pediatric Brain Tumor Fund
- Medical Service of the Department of Veterans Affairs
- American Asthma Society
- [R01 CA134659]
- [R01 CA112356]
- [R01 CA103828]
- [R01 CA148633]
- [R01 CA135401]
- [R01 DK082690]
Prostaglandins derived from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis. COX-2 inhibitors, which block the formation of prostaglandins, suppress tumor growth, whereas sEH inhibitors, which increase endogenous EETs, stimulate primary tumor growth and metastasis. However, the functional interactions of these two pathways in cancer are unknown. Using pharmacological inhibitors as probes, we show here that dual inhibition of COX-2 and sEH synergistically inhibits primary tumor growth and metastasis by suppressing tumor angiogenesis. COX-2/sEH dual pharmacological inhibitors also potently suppress primary tumor growth and metastasis by inhibiting tumor angiogenesis via selective inhibition of endothelial cell proliferation. These results demonstrate a critical interaction of these two lipid metabolism pathways on tumorigenesis and suggest dual inhibition of COX-2 and sEH as a potential therapeutic strategy for cancer therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据