大黄素抑制胰腺癌裸鼠原位移植瘤新生血管形成的机制研究

Effect of emodin on neovascularization of orthotopically implanted human pancreatic cancer in nude mice and its mechanism

目的探讨大黄素对胰腺癌SW1990细胞裸鼠原位移植瘤新生血管的影响及其作用机制。方法建立胰腺癌SW1990细胞裸鼠原位移植瘤动物模型,分为对照组(N组)、大黄素低剂量组(20mg/kg,E20组)、大黄素中剂量组(40mg/kg,E40组)以及大黄素高剂量组(80mg/kg,E80组)。各组均采取腹腔注射给药,每周3次,共2周,观察药物对移植瘤生长的影响。采用免疫组化染色法检测肿瘤组织CD31的表达和微血管密度(MVD)。采用RT-qPCR法和Western blot法检测肿瘤血管生成素1(Ang-1)、血管生成素2(Ang-2)、酪氨酸激酶受体2(Tie-2)及血管内皮生产因子(VEGF)的表达。结果末次用药后1周,大黄素组MVD较对照组降低(P<0.05),且MVD与大黄素用药浓度呈负相关(P<0.05);大黄素组Ang-1、Ang-2、Tie-2及VEGF的表达较对照组减少(P<0.05)。结论大黄素对胰腺癌SW1990细胞裸鼠原位移植瘤的新生血管有抑制作用,其机制可能是大黄素改变新生血管相关的Ang-1、Ang-2、Tie-2及VEGF的表达。

Objective To investigate the effect of emodin on tumor neovascularization of orthotropically implanted pancreatic cancer in nude mice and its mechanism.Methods Human pancreatic cancer SW1990 cells were orthotropically implanted in 40 nude mice,and the mice were randomly divided into 4 groups with 10 in each group.Emodin was injected intraperitoneally 3 times a week for 2 weeks at dose of 0mg/kg(Group N),20mg/kg(Group E20),40mg/kg(E40 Group)or 80 mg/kg(Group E80),respectively.The tumor growth was observed.The expression of the CD31 was detected by immunochemistry,the micro vessel density(MVD)was calculated.RT-qPCR and Western blot were performed to detect the expression of Ang-1,Ang-2,Tie-2 and VEGF mRNA and protein,respectively.Results At the end of experiments the MVD in emodin treatment groups was significant lower than that of the control group(P<0.05),while MVD was negatively correlated with the emodin dose(P<0.05).Expression of Ang-1,Ang-2,Tie-2 and VEGF of the emodin treatment groups was decreased compared with the control group(P<0.05).Conclusion Emodin can inhibit neovascularization of orthotopically implanted human pancreatic cancer in nude mice,which may be related to down-regulated expression of the angiogenesis-associated factors Ang-1,Ang-2,Tie-2 and VEGF.