Objective:Angiogenesis plays a major role in the pathogenesis of many disorders.Vascular endothelial growth factor(VEGF) has been shown to be the key regulator of normal and pathological angiogenesis.Many studies showed that decreased expression of VEGF has been inhibited growth and migration of cancer cells.The aim of this study was to explore the effects of Betulinic acid on the VEGF expression and the growth of colorectal cell SW480 xenografts in nude mice.Methods:The xenografts derived from colorectal cell SW480 were established in BALB/C nude mice.Inoculated mice were randomly divided into negative control(corn oil), low dose betulinic acid group(20 mg/kg/d) and high dose group(40 mg/kg/d).After 22 days, the animals were sacrificed;tumor volume and weights were measured.The mRNA level of VEGF was analyzed by quantitative real-time polymerase chain reaction.The expression of VEGF protein was detected by immunohistochemistry.Results:The tumor weight was significantly lower in low and high dose groups than in corn oil group(1.12 ± 0.04, 0.43 ± 0.02 vs 2.08 ± 0.07;P < 0.05).The mRNA levels of VEGF was also significantly lower in betulinic acid treated groups(0.72 ± 0.02, 0.38 ± 0.01;P < 0.05) than in control group(1.08 ± 0.04).H&E staining showed tumor tissue necrosis was observed in treatment groups.The positive expression of VEGF was lower in low and high dose groups than in corn oil group.Gray scale increased in low dose group and high dose group(121.1 ± 2.8, 156.2 ± 3.3, P < 0.05).Conclusion:Betulinic acid had significant inhibitory effect on VEGF expression and tumors growth of human colorectal cancer xenografts in vivo, and down-regulation of VEGF expression may account for one of the molecular mechanisms of the anticancer effects of betulinic acid.
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