JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats.
JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats.
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DOI：
10.1186/1471-2407-5-26
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发表时间：
2005-03-03
期刊：
影响因子：
3.8
通讯作者：
Sugihara K
中科院分区：
文献类型：
--
作者：
Kobayashi H;Uetake H;Higuchi T;Enomoto M;Sugihara K
流行病学研究表明，经常服用NSAID的人与结直肠癌相关的死亡率较低。由于考克斯-2抑制剂通过某些机制阻止肿瘤生长，我们评估了JTE-522（一种选择性考克斯-2抑制剂）对大鼠结肠癌肺转移的影响。将5 × 106 RCN-9（大鼠结肠癌细胞）混悬液注射到24只麻醉雄性F344/DuCrj大鼠的尾静脉中。从RCN-9注射前一天至研究结束，口服JTE-522（0、3、10或30 mg/kg/天）。24天后，从处死的大鼠中取出肺并称重。在最大横截面中对肺转移性肿瘤进行显微镜评价。我们还对考克斯-2和VEGF进行了免疫组织化学染色。JTE-522剂量依赖性地降低肺重量（p = 0.001）和肺转移性肿瘤的大小（p = 0.0002）。但各组间转移瘤数差异无统计学意义。未检测到JTE-522的显著不良反应。免疫组化显示肺转移瘤中考克斯-2和VEGF均呈高水平表达。JTE-522剂量依赖性地减少肺转移瘤的大小，但不减少肺转移瘤的数量。考克斯-2抑制剂可能阻断转移性肿瘤生长，但不能阻断实际转移。选择性考克斯-2抑制剂可用作抑制转移性肿瘤生长以及结直肠癌肿瘤发生的治疗剂。
Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model. A suspension of 5 × 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.
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影响因子：
8.8
作者：
Tomozawa, S;Nagawa, H;Muto, T
通讯作者：
Muto, T
影响因子：
29.4
作者：
Fenwick, SW;Toogood, GJ;Hull, MA
通讯作者：
Hull, MA
影响因子：
3.3
作者：
Muto, Tetsuichiro;Kotake, Kenjiro;Koyama, Yasuo
通讯作者：
Koyama, Yasuo
影响因子：
158.5
作者：
THUN, MJ;NAMBOODIRI, MM;HEATH, CW
通讯作者：
HEATH, CW
DOI：
10.1165/ajrcmb.18.6.2980
发表时间：
1998-06-01
影响因子：
6.4
作者：
Christou, H;Yoshida, A;Kourembanas, S
通讯作者：
Kourembanas, S