Skip to Content
Merck
  • Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis.

Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis.

Proceedings of the National Academy of Sciences of the United States of America (2014-07-16)
Guodong Zhang, Dipak Panigrahy, Sung Hee Hwang, Jun Yang, Lisa M Mahakian, Hiromi I Wettersten, Jun-Yan Liu, Yanru Wang, Elizabeth S Ingham, Sarah Tam, Mark W Kieran, Robert H Weiss, Katherine W Ferrara, Bruce D Hammock
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mouse VEGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Mouse VEGF ELISA Kit, for serum, plasma, cell culture supernatant
Sigma-Aldrich
Rat VEGF ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Rat VEGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Human VEGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Human VEGF R2 ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Human VEGF R3 ELISA Kit, for serum, plasma, cell culture supernatant, urine
Sigma-Aldrich
Human VEGF-A ELISA Kit, for serum, plasma, cell culture supernatants and urine