Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma cell proliferation and tumor growth. Anticancer Res 2009 Oct;29(10):3819-24
Date
10/23/2009Pubmed ID
19846914Pubmed Central ID
PMC2807614Scopus ID
2-s2.0-71949116212 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
BACKGROUND: We examined the ability of inhibitors of the synthesis or actions of 20-HETE, metabolite of arachidonic acid, to inhibit proliferation of human renal carcinoma cell lines.
MATERIALS AND METHODS: 786-O and 769-P cells were exposed to either 10 microM HET0016 (selective inhibitor of 20-HETE synthesis), 10 microM WIT002 (20-HETE antagonist), or vehicle. Subsequently, we assessed the effect of WIT002 on tumor growth in vivo using an ectopic mouse model of clear-cell renal carcinoma.
RESULTS: Addition of HET0016 and WIT002 inhibited the proliferation of 786-O and 769-P human renal cell carcinoma lines. HET0016 and WIT002 had little effect on the proliferation of primary cultures of normal human proximal tubule epithelial cells. WIT002 (10 mg/kg, s.c.) administered daily to athymic nude mice implanted subcutaneously with 786-O cells reduced the growth of the tumors by 84 % compared to vehicle (p<0.001).
CONCLUSION: 20-HETE is required for proliferation of human renal epithelial cancer.
Author List
Alexanian A, Rufanova VA, Miller B, Flasch A, Roman RJ, Sorokin AAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmidinesAnimals
Arachidonic Acid
Carcinoma, Renal Cell
Cell Growth Processes
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 4
Down-Regulation
Humans
Hydroxyeicosatetraenoic Acids
Kidney Neoplasms
Mice
Mice, Nude
RNA, Messenger
TNF-Related Apoptosis-Inducing Ligand
Xenograft Model Antitumor Assays
