[A relationship between cyclooxygenase-2 expression and tumor angiogenesis in experimental rat liver carcinogenesis].
OBJECTIVE
To explore the relationship between the expression of cyclooxygenase-2 (COX-2) and angiogenesis in hepatocellular carcinoma.


METHODS
Forty Wistar rats were divided into two groups: a model group (30 rats) and a normal group (10 rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN) in the model group rats. The rats were sacrificed in batches at the 6th, 12th and 18th week of the experiment. Histological sections of liver tissues were made using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2 protein in the liver tissues were evaluated using immunohistochemical methods.


RESULTS
In liver sections from the model group there were marked pathological changes (steatosis, cell infiltration, cirrhosis and liver cancer). The expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were remarkably increased during the hepatocellular carcinogenesis. Microvessel density (MVD) was also obviously raised during the process of the cancer development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2 (r=0.858, 0.788, 0.684, respectively; all P less than 0.01). There was also a direct correlation between the COX-2 and VEGF/KDR/MMP-2/MVD (r=0.771, 0.599, 0.690, 0.788, respectively; all P < 0.01).


CONCLUSIONS
COX-2 can promote tumor angiogenesis during rat hepatocellular carcinogenesis. This may be one of the mechanisms in which COX-2 promotes carcinomas.
Xie
Ying-hui
YH
Department of Gastroenterology, Qilu Hospital of Shandong University, Jionan 250012, China. xieyh@sdu.edu.cn
Yuan
Meng-biao
MB
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic; D051381:Rats; D017208:Rats, Wistar
D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat