蟾毒灵对裸鼠人结肠癌血管新生相关VEGFA蛋白表达的影响

目的:通过实验研究观察蟾毒灵对人结肠癌血管新生的作用。方法:CCK-8法检测不同浓度蟾毒灵对人脐静脉内皮细胞增殖的影响;构建裸鼠人结肠癌移植瘤模型,随机分为对照组(0.9%生理盐水)、蟾毒灵组(1.5 mg·kg~(~(-1))·d~(-1)),药物干预4周后,观察各组裸鼠移植瘤瘤体生长情况,Western blot检测瘤体组织中血管内皮生长因子A(VEGFA)的表达。结果:蟾毒灵在2.5~320.0 ng/ml的浓度区间内,其对人脐静脉内皮细胞的生长抑制率为1.67%~95.40%,IC50为20.86 ng/ml,呈剂量依赖性。蟾毒灵组裸鼠移植瘤瘤体明显小于对照组(P0.01),蟾毒灵组瘤体中VEGFA蛋白的表达明显低于对照组(P0.05)。结论:蟾毒灵可抑制血管内皮细胞增殖,抑制裸鼠人结肠癌移植瘤瘤体的生长,其机制可能与下调VEGFA蛋白的表达有关。

Effects of Bufalin on the Protein Expression of Human Colorectal Cancer Angiogenesis Related VEGFA in Nude Mice

  Objective:To investigate the effects of bufalin on human colorectal cancer angiogenesis.   Methods: The effects of bufalin at different concentration on proliferation of human umbilical vein endothelial cells were detected by CCK-8 method.Transplanted tumor model of human colorectal cancer was established in nude mice,and then the mice were randomly divided into the control group which treated with normal saline and the bufalin group which treated with bufalin at the dose of 1.5 mg/kg a day. After drug intervention for 4 weeks,the growth of transplanted tumor in nude mice was observed,the expression of vascular endothelial growth factor A (VEGFA) in tumor tissues was detected by Western blot.   Results: In the concentration range of 2.5-320.0 ng/ml,the growth inhibition rate of bufalin on human umbilical vein endothelial cells was 1.67%-95.40%,which showed in a dose-dependent manner, IC₅₀ was 20.86 ng/ml. The transplanted tumor in nude mice of the bufalin group was significantly smaller than that of the control group(P<0.01). The protein expression of VEGFA in tumor tissues of the bufalin group was significantly lower than that of the control group(P<0.05).   Conclusion: Bufalin could inhibit the proliferation of vascular endothelial cells and the tumor growth in nude mice transplanted with human colorectal cancer.Its mechanism may be related to down-regulating the protein expression of VEGFA.