Abstract:

Objective To investigate the influence of angiotensin Ⅱ type 1 receptor blocker candesartan on growth and angiogenesis of mice bearing human hepatocellular carcinoma xenograft.Methods Fourty-eight mice bearing H22 hepatocellular carcinoma xenograft were established and randomly divided into normal saline group，low-dose candesartan group（2mg／kg），high-dose candesartan group（20mg／kg）and flurouracil group（25mg／kg）with 12 in each group. Nine days after administration， the mice were sacrificed， and the weight of transplanted tumors was measured to calculate the tumor inhibitory rate. The immunohistochemical technology was adopted to detect the expressions of vascular endothelial growth factor（VEGF） and CD34 to calculate microvessel density（MVD）. The same test was applied to 40 mice to observe the survival time and calculate the life extension rate. Results The tumor inhibition rates in highdose candesartan group（35.3％）and fluorouracil group（50.6％） were higher than 20.7％ in low-dose candesartan group（P＜0.05）. Compared with the normal saline group，significant reduction of VEGF expression was observed in lowdose（5.083±1.240） and high-dose candesartan（4.083±1.165） with significance（P＜0.05）. VEGF score in high-dose candesartan was lower than that in low-dose candesartan（P＜0.05）. Compared with the normal saline group， the MVD in low-dose（20.633±2.171） and high-dose candesartan groups（17.150±2.713） were significantly reduced（P＜0.01）. Compared with low-dose candesartan group， the MVD in highdose candesartan group were significantly reduced（P＜0.05）. The life extension rates in low-dose candesartan group（20.4％） was lower than 39.5％ in high-dose candesartan group and 30.6％ in fluorouracil group（P＜0.05）. Conclusion Candesartan is effective in inhibiting the growth of hepatocellular carcinoma xenograft， and the possible mechanism may be related to the inhibition of angiogenesis.