Effect of Sorafenib in Increased VEGF in Stimulating Effect of Walker-256 Transplanted Liver Cancer Model in SD Rats / 中山大学学报(医学科学版)

ABSTRACT

[Objective] To investigate association between the time point of sorafenib administered and suppress effect on tumor growth secondary to the increased expression of vascular endothelial growth factor (VEGF).[Methods] Fifty SD rats were performed intrahepatic implantation using tumor tissues from subcutaneous tumors in nude mice which were administered Walker 256 tumor cells.Ten days after the procedure,MR scans were used to choose forty SD rats with successful hepatic tumor transplantation among fifty experimental animals.Then they were randomly divided into four groups(A,control group) mere injection of vascular endothelial growth factor (VEGF);(B) administration of sorafenib 72 hours prior to VEGF injection;(C) administration of sorafenib together with VEGF injection;(D) administration of sorafenib 72 hours later to VEGF injection.The tumor growth and median survival time of rodents were observed and compared.After each experimental animal died,immunohistochemical (IHC) methods were applied to detect the expression of VEGF in tumors.[Results] Ten days after the administration of sorafenib,MR showed significant growth of hepatic tumors,the tumor size in experiment group were significiant smaller,than control group (5.4 cm) with statistical significance.Median survival time of four groups were (19.6 ± 1.8) d,(31.2 ± 7.0) d,(27.4 ± 4.9) d,and (26.5 ± 4.6) d,respectively,which indicated that animals in sorafenib groups lived longer than those in control group (P ＜ 0.05).Differences can be obseverd in sorafenib groups with statistical significance existing (P ＜ 0.05).Harvest hepatic tumor tissues from dead animals and HE staining as well as IHC examination were performed.The expression of VEGF in four groups were 88.3 ± 13.6,42.8 ± 8.0,71.9 ± 15.7,and 73.6 ± 13.7.There were statistical significance between control group and sorafenib groups.And further in sorafenib groups,the expressions of VEGF also varied greatly.[Conclusion] Sorafenib can extend the survival time,reduce tumor angiogenesis.And we can conclude that administration of sorafenib before the transient increased expression of VEGF offers survival benefits than that after the evaluation of VEGF levels.