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Cyclooxygenase
Inhibitors Suppress Angiogenesis and Reduce Tumor Growth In Vivo |
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Hitoshi Sawaoka,
Shingo Tsuji, Masahiko Tsujii, Edhi S. Gunawan, Yutaka Sasaki, Sunao Kawano,
and Masatsugu Hori |
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Department
of Internal Medicine and Therapeutics (HS, ST, MT, ESG, YS, MH), Oska Univesity
Graduate School of Medicine; and Department of Clinical Laboratory Science
(SK), School of Allied Health Sciences, Osaka University Faculty of Medicine,
Suita, Japan |
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SUMMARY: Angiogenesis plays
a key role in the development of malignant tumors. To clarify the roles
of cyclooxygenase (COX) in malignant tumor development and angiogenesis,
we investigated the effects of COX inhibitors on two kinds of gastrointestinal
cancer xenograft, one of which overexpresses COX-2 and the other expresses
no COX, in nude mice in vivo. There was a positive correlation between tumor
volume and angiogenesis within the xenograft. Oral administration with a
specific COX-2 or a nonspecific COX inhibitors lowered the expression of
potent angiogenic factors; vascular endothelial growth factor and basic
fibroblast growth factor, reduced angiogenesis and growth, induced apoptosis,
and suppressed cell replication of the COX-2 overexpressing cancer xenografts
in a dose-dependent manner. A nonspecific COX inhibitor, not a specific
COX-2 inhibitor, reduced growth and angiogenesis of non-COX expressing cancer
xenograft by inhibition of COX-1 in vascular endothelial cells. These results
demonstrate that COX inhibitors suppress angiogenesis and tumor growth by
inhibiting expression of angiogenic factors and vascular endothelial cell
growth. They support the hypothesis that COX plays an important role in
cancer growth via angiogenesis. These findings offer a new strategy against
cancer using COX inhibitors (nonsteroidal anti-inflammatory drugs). |
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