The effect of meloxicam, a selective COX-2 inhibitor, on the microvasculature of small metastatic liver tumors in rats.
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.
Iwase
Naoko
N
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. inao441122@jcom.home.ne.jp
Higuchi
Tetsuro
T
Gonda
Tsuyoshi
T
Kobayashi
Hirotoshi
H
Uetake
Hiroyuki
H
Enomoto
Masayuki
M
Sugihara
Kenichi
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary*; D008297:Male; D000077239:Meloxicam; D008833:Microcirculation / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011916:Rats, Inbred F344; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam