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JTE‐522, a selective COX‐2 inhibitor, interferes with the growth of lung metastases from colorectal cancer in rats due to inhibition of neovascularization: A vascular cast model study
Author(s) -
Kobayashi Hirotoshi,
Gonda Tsuyoshi,
Uetake Hiroyuki,
Higuchi Tetsuro,
Enomoto Masayuki,
Sugihara Kenichi
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20523
Subject(s) - medicine , angiogenesis , neovascularization , metastasis , colorectal cancer , lung , vascularity , pathology , lung cancer , cancer , cancer research
Abstract The lung is a frequent site of metastasis from colorectal cancer, but angiogenesis of lung metastases has not been clarified. Some COX‐2 inhibitors prevent tumor growth, although the inhibitory mechanism at the metastatic site is obscure. We investigated the microvascular structure of small lung metastases and the effect of JTE‐522, a selective COX‐2 inhibitor, on the angiogenesis of pulmonary metastases from colorectal cancer in rats. The tail veins of 25 male F344/DuCrj rats, aged 5 weeks, were injected with a tumor suspension containing 5 × 10 6 RCN‐9, a rat colon cancer cell line. Three weeks later, pulmonary vascular resin corrosion casts were taken and the vascularity of metastases was studied using stereo and scanning electron microscopes. We investigated the effect of 0, 10 and 30 mg/kg/day of JTE‐522 on the angiogenesis of pulmonary metastases in 3 groups of 5 male rats out of 25. JTE‐522 reduced the diameter of tumor vessels as well as the number and size of metastatic tumors. The diameter of tumor vessels and the size of lung metastases significantly and positively correlated with neovascularization in the control group, but not in the JTE‐522‐treated groups. JTE‐522 also affected type of vasculature of metastases, which differed depending on their size. JTE‐522 interfered with the growth of hematogenous metastatic tumors by disrupting neovascularization. However, JTE‐522 may have some important mechanisms other than inhibition of neovascularization. JTE‐522 may be one of the therapeutic agents for the treatment of hematogenous metastasis of colorectal cancer. © 2004 Wiley‐Liss, Inc.