Japanese Journal of Clinical Oncology Advance Access originally published online on August 27, 2007
Japanese Journal of Clinical Oncology 2007 37(9):673-678; doi:10.1093/jjco/hym081
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© 2007 Foundation for Promotion of Cancer Research
The Effect of Meloxicam, a Selective COX-2 Inhibitor, on the Microvasculature of Small Metastatic Liver Tumors in Rats
1 Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo
2 Department of Surgery, Saitama Medical Center, Saitama Medical School, Kawagoe, Saitama, Japan
For reprints and all correspondence: Naoko Iwase, Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: inao441122{at}jcom.home.ne.jp
Received October 12, 2006; accepted April 23, 2007
Background: COX-2 is involved in tumor angiogenesis and modulation of the production of angiogenetic factors by colorectal carcinoma cells. It has been shown that COX-2 inhibitors have inhibitory activities against various types of tumor, including colorectal carcinoma. In this study, we investigated the tumor vessels of small metastatic liver tumors in rats and the effect of meloxicam, a selective COX-2 inhibitor, on their growth and microvasculature.
Methods: The metastatic liver tumors were produced by intraportal inoculation of RCN-H4 cells in male F344/DuCrj rats (n = 40). The microvasculature was examined by scanning electron microscopy and stereomicroscopy. Microvascular casts were produced by perfusion via the abdominal aorta 14 days after tumor inoculation. Four groups (control, groups 1–3) of rats were treated with meloxicam 0, 0.6, 1.0 and 3.0 mg/kg/day, respectively, by oral gavage 5 days/week for two weeks from the day of inoculation of RCN-H4 cells.
Results: The mean number of tumors was significantly decreased in groups 1–3 (5.6±0.8 standard deviation, SD; 3.6±1.1; and 5.5±1.1, respectively) compared with control (11.2±2.7; P = 0.0002, each). Meloxicam also significantly reduced the mean diameter of the tumor: 730±254, 685±212 and 644±139 in groups 1–3, respectively, in comparison with 870±276 in control (P = 0.0025, 0.0011 and <0.0001, respectively).
Conclusions: Meloxicam's anti-angiogenic activity interferes with the growth of metastatic liver tumors. Meloxicam might have therapeutic potential for liver metastasis of colorectal carcinoma.
Key Words: COX-2 • colorectal carcinoma • liver metastasis • microvasculature