参一胶囊联合5-氟尿嘧啶对小鼠结肠癌血管生成抑制作用的机制研究

Inhibitory effect of Shenyi capsule combined with 5-fluorouracil on the angiogenesis in mouse colon cancer

目的探讨参一胶囊联合5-氟尿嘧啶(5-fluorouracil,5-FU)对结肠癌生长、血管生成的抑制作用及可能的机制。方法建立BALB/c小鼠Lo Vo结肠癌模型50只,随机分为5组,根据处理方式的不同分为模型组、5-FU组、参一胶囊低剂量组、参一胶囊高剂量组、参一胶囊+5-FU组。检测记录各组小鼠肿瘤体积、肿瘤微血管密度(microvessel density,MVD)、免疫器官变化,采用Western-Blot法检测瘤体Gli1、VEGF蛋白蛋白表达。结果 1)与模型组相比,各治疗组小鼠的肿瘤体积均受到明显抑制。参一胶囊高剂量组、参一胶囊+5-Fu组的抑瘤率最高,且随着给药时间的延长,这种抑制优势愈加明显。(2)与模型组比较,5-FU组小鼠的免疫器官质量及指数出现降低,其余各治疗组均有不同程度提高。参一胶囊+5-FU组的胸腺质量、胸腺指数、脾质量、脾指数改善最为显著,明显好于所有其他治疗组(P<0. 05)。(3)参一胶囊+5-FU组对MVD的抑制作用最明显,参一胶囊高剂量组次之,低剂量组抑制更弱,单纯5-FU组对肿瘤MVD无明显影响。(4)与模型组相比,5-FU组、参一胶囊低剂量组小鼠各种类型的结肠癌转移均未表现出明显的抑制作用(P>0. 05)。高剂量参一胶囊组、参一胶囊+5-FU组小鼠的结肠癌各器官转移率均显著降低(P<0. 05)。(5) Western blot检测结果显示,与模型组相比,5-FU组及参一胶囊低剂量组小鼠的Gli1蛋白、VEGF蛋白表达量均较低,但差异无显著性(P>0. 05)。参一胶囊高剂量组、参一胶囊+5-FU组的Gli1蛋白、VEGF蛋白表达量则显著降低(P<0. 05)。结论参一胶囊对结肠癌细胞的生长及血管生成均有明显的抑制作用,这种抑制作用在于5-FU配伍应用时更为显著,Hedgeog-Glin1信号通路相关的VEGF表达可能是其主要的作用靶点。

Objective To investigate the inhibitory effect of Shenyi capsules combined with 5-FU on the growth and angiogenesis of colon cancer and its possible mechanism.Methods Fifty BALB/c mice with LoVo colon cancer were randomly divided into five groups:model group,5-FU group,Shenyi capsule low-dose group,Shenyi capsule high-dose group,and Shenyi capsule+5-FU group.Differences in disease indicators were compared.Results 1)The Shenyi capsule high-dose and Shenyi capsule+5-Fu groups had the highest inhibition rate,and with the extension of administration time,the inhibition was more marked.(2)The thymus mass,thymus index,spleen mass and spleen index of the Shenyi capsule+5-FU group were improved significantly(P<0.05).(3)The inhibitory effect in the Shenyi capsule+5-FU group on MVD was the most obvious,followed by the Shenyi capsule high-dose group and low-dose group.An inhibitory effect of Shenyi capsule+5-FU group on the MVD of tumor was not observed.(4)Compared with the model group,the metastasis rates in various organs in the high dose Shenyi capsule group and Shenyi capsule+5-FU group were significantly lower(P<0.05).(5)Compared with the model group,the expressions of Gli1 protein and VEGF protein were decreased significantly(P<0.05)in the Shenyi capsule high-dose group and Shenyi capsule+5-FU group.Conclusions Shenyi capsule inhibits the growth and angiogenesis of colon cancer cells,and VEGF may be its main target.