Effect of application of Sorafenib on rat with Walker-256 hepatoma

Abstract

Objective To investigate the effect and mechanism of application of Sorafenib on rat with Walker-256 hepatoma. Methods Walker-256 hepatoma rats were randomly divided into 4 groups(n=16): Control group(group A), Sorafenib low-dose group(group B), Sorafenib middle-dose group(group C), Sorafenib high-dose group(group D), and normal group(group E, n=8). Eight rats of each group were chosen 20 days after operation to test the alanine amino transferase(ALT), aspartate aminotransferase(AST) and bilirubin (TB) of vein blood. Weight and size of liver tumor block were measured, then the quality inhibition rate and size inhibition rate were calculated. Observations of pathological changes in tumor adjacent tissues were made with hematoxylineosin sectioning(HE), vascular endothelial growth factor(VEGF) and microvessel density(MVD) level of tumor adjacent tissues were detected by immunohistochemistry, and bivariate correlation analysis of VEGF and MVD were used to identify their relationship. Survival time of remaining 8 rats of control group and each experimental group were observed. Results The serum level of ALT, AST, TB in experimental group were generally lower than that of control group, P<0.05. Tumor volume and quality of middle-dose group and high-dose group were smaller than control group, P<0.05. Compared with control group, Sorafenib experimental groups had signifcantly higher ratio of cancer cell apoptosis, lower ratio of necrosis of liver cells, VEGF-positive rate and MVD counts were smaller, P<0.01. VEGF and MVD were highly correlated, P<0.01, rp=0.843. Survival ratio of group C and D were higher, P<0.05. Conclusions Sorafenib could inhibit synthesis of VEGF in tumor tissue, which inhibit angiogenesis of tumor, then tumor growth, as well as invasion to normal liver cells are inhibited, and liver function damage are slighter, survival time are prolonged, which result to a positive therapeutic effect of application of Sorafenib on rat with Walker-256 hepatoma. Key words: Rat; Liver cancer; Sorafenib; Walker-256 cancer cell