Abstract | BACKGROUND: 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.
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Authors | Anna Alexanian, Victoriya A Rufanova, Bradley Miller, Averia Flasch, Richard J Roman, Andrey Sorokin |
Journal | Anticancer research
(Anticancer Res)
Vol. 29
Issue 10
Pg. 3819-24
(Oct 2009)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 19846914
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amidines
- HET0016
- Hydroxyeicosatetraenoic Acids
- RNA, Messenger
- TNF-Related Apoptosis-Inducing Ligand
- Arachidonic Acid
- 20-hydroxy-5,8,11,14-eicosatetraenoic acid
- Cytochrome P-450 Enzyme System
- Cytochrome P450 Family 4
- CYP4F2 protein, human
- CYP4F3 protein, human
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Topics |
- Amidines
(pharmacology)
- Animals
- Arachidonic Acid
(metabolism)
- Carcinoma, Renal Cell
(drug therapy, metabolism, pathology)
- Cell Growth Processes
(drug effects, physiology)
- Cytochrome P-450 Enzyme System
(biosynthesis, genetics)
- Cytochrome P450 Family 4
- Down-Regulation
(drug effects)
- Humans
- Hydroxyeicosatetraenoic Acids
(antagonists & inhibitors, biosynthesis, pharmacology)
- Kidney Neoplasms
(drug therapy, metabolism, pathology)
- Mice
- Mice, Nude
- RNA, Messenger
(biosynthesis, genetics)
- TNF-Related Apoptosis-Inducing Ligand
(pharmacology)
- Xenograft Model Antitumor Assays
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