%0 Journal Article
%T JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats
%A Hirotoshi Kobayashi
%A Hiroyuki Uetake
%A Tetsuro Higuchi
%A Masayuki Enomoto
%A Kenichi Sugihara
%J BMC Cancer
%D 2005
%I BioMed Central
%R 10.1186/1471-2407-5-26
%X A suspension of 5 กม 106 RCN-9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF.JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of pulmonary metastatic tumors (p = 0.0002). However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors.JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer.Colorectal cancer is a widespread fatal malignancy in the West [1] and its incidence in Japan is increasing [2]. Epidemiological studies have shown that regular doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with lower rates of colorectal polyps, colorectal cancer, and colorectal cancer-associated mortality. Waddell and Loughry initially reported that sulindac decreased the number of polyps in patients with familial adenomatous polyposis (FAP) [3]. The largest study of aspirin and colon cancer was undertaken by Thun et al. in 1991 [4]. They found that colon cancer mortality decreased among those who used aspirin, and that the protective effect was increased by increasing doses. NSAIDs inhibit prostaglandin production mainly by inhibiting cyclooxygenase (COX) that is expre
%U http://www.biomedcentral.com/1471-2407/5/26