Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth invivo

Angiogenesis plays a key role in the development of malignant tumors. To cl arify 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 th e other expresses no COX, in nude mice in vivo. There was a positive correl ation between tumor volume and angiogenesis within the xenograft. Oral admi nistration with a specific COX-2 or a nonspecific COX inhibitors lowered th e expression of potent angiogenic factors; vascular endothelial growth fact or and basic fibroblast growth factor, reduced angiogenesis and growth, ind uced 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-I in vascular endothelial cells. These results demonstrate that COX inhibitors suppress angiogenesis and tumor growth by inhibiting expression of angiogenic factors and vascul ar endothelial cell growth. They support the hypothesis that COX plays an i mportant role in cancer growth via angiogenesis. These findings offer a new strategy against cancer using COX inhibitors (nonsteroidal anti-inflammato ry drugs).