Correlation between angiogenic/inflammatory mediators in Wister rat model of liver dysplasia

Angiogenesis plays a critical role in tumor development and progression. It is regulated through the elaboration of many inflammatory/angiogenic mediators. In this study, we followed angiogenesis in hepatocarcinogenesis process from cancer initiation to sever dysplasia by measuring several inflammatory/angiogenic mediators. Wister rat model of liver cancer was set up using diethylnitrosamine (DEN). One hundred twenty rats were divided into 7 groups: normal untreated and 1- to 6-month DEN-treated animals. Every month, group of DEN-treated animals were sacrificed. Histopathological examination of livers was done. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF and PDGF), interleukin-8 (IL-8), IL-4, tumor necrosis factor (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay (ELISA). Histopathological findings were confirmatory to the gradual formation of liver cancer with time (from mild to moderate to irreversible severe dysplasia). Increase in angiogenic (VEGF and IL-8) (P < 0.001) and inflammatory (IL-4 and COX-2) (P < 0.001) mediators were observed. Elevation in TNF-α and PDGF secretion levels was recorded after 3 months of DEN injection (P < 0.001). Our data stressed on the importance of inflammation/angiogenesis processes in dysplasia. The exact regulatory mechanisms of liver cancer remain to be clarified.