Abstract | PURPOSE: To assess the role of phosphatidylinositol-3 kinase (PI3K) inhibition in vascular permeability, angiogenesis, and vascular remodeling in tumor vessels and peritoneal lining in an athymic mouse model of i.p. human ovarian carcinoma. EXPERIMENTAL DESIGN: Mice were inoculated i.p. with cells from the human ovarian cancer cell line, OVCAR-3. Fourteen days after inoculation, mice were treated with or without the PI3K inhibitor LY294002, 3 days weekly for 4 weeks. At the end of the experiment, some mice were anesthetized and injected via the tail vein with FITC-labeled lycopersicon lectin and perfused through the aorta before sacrifice. The peritoneal wall and tumor from all mice were removed and embedded in 10% agarose. Tumor sections were visualized by fluorescence microscopy. RESULTS:
Ascites in the LY294002-treated group (0.69 +/- 0.27 mL) was reduced by 72.4% compared with the control group (2.5 +/- 1.2 mL). Tumor burden in the LY294002-treated group (0.62 +/- 0.32 g) was reduced by 47.3% compared with the control group (1.18 +/- 0.41 g). LY294002 inhibited peritoneal and tumor vascularization resulting in numerous leaky, irregular, tortuous vessels in scant, straight, relatively impermeable vessels. CONCLUSIONS:
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Authors | Limin Hu, Judith Hofmann, Robert B Jaffe |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 22
Pg. 8208-12
(Nov 15 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 16299254
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromones
- Enzyme Inhibitors
- Morpholines
- Phosphoinositide-3 Kinase Inhibitors
- Vascular Endothelial Growth Factor A
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Topics |
- Animals
- Ascites
(metabolism)
- Capillary Permeability
- Cell Line, Tumor
- Chromones
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Female
- Humans
- Immunohistochemistry
- Mice
- Mice, Nude
- Microscopy, Fluorescence
- Morpholines
(pharmacology)
- Neovascularization, Pathologic
- Ovarian Neoplasms
(blood supply, pathology, prevention & control)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphoinositide-3 Kinase Inhibitors
- Vascular Endothelial Growth Factor A
(analysis)
- Xenograft Model Antitumor Assays
(methods)
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