辣椒素抑制Lewis 肺癌小鼠血管生成的实验研究

Inhibitory effect of capsaicin on angiogenesis in Lewis lung cancer of mice

摘要:

目的 观察辣椒素对Lewis 肺癌小鼠血管生成的影响，并探讨其可能的机制。方法 复制Lewis肺癌小鼠模型，随机分为模型组，辣椒素低、中、高剂量组，以及阳性对照组5 组，每组9 只。各组连续用药20 d，于末次给药后处死全部小鼠，比较各组小鼠瘤体积、瘤重、抑瘤率及微血管密度（MVD）。采用免疫组织化学法检测CD34 阳性细胞率；采用Western blot 和实时荧光定量聚合酶链反应检测缺氧诱导因子1α（HIF-1α）、血管内皮生长因子（VEGF）蛋白和mRNA 表达的变化。结果 与模型组比较，辣椒素抑制Lewis 肺癌小鼠瘤体积、瘤重、MVD 和CD34 阳性细胞率（P <0.05）；与模型组比较，辣椒素抑制Lewis 肺癌小鼠HIF-1α、VEGF 蛋白和mRNA 的表达（P <0.05）。结论 辣椒素抑制Lewis 肺癌小鼠肿瘤生长和血管生成，其机制可能与抑制HIF-1α 和VEGF 的表达有关。

Abstract:

Objective To investigate the effect of capsaicin on angiogenesis in Lewis lung cancer of mice, and to discuss its possible mechanism. Methods The mice with transplanted Lewis lung cancer were randomly divided into 5 groups (9 in each): model group, low-dosage capsaicin group, medium-dosage capsaicin group, high-dosage capsaicin group, and positive control group. After continuous medication for 20 days, the mice were sacrificed. The tumor volume, tumor weight, tumor inhibitory rate and microvessel density (MVD) were compared among the 5 groups. The rate of CD34+ cells was detected by immunohistochemical analysis. The mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by qRT-PCR and Western blot respectively. Results Capsaicin significantly inhibited the tumor volume and weight, MVD and the rate of CD34+ cells compared with the model group (P < 0.05). Capsaicin also significantly inhibited the mRNA and protein expressions of HIF-1α and VEGF in the Lewis lung cancer of mice compared with the model group (P < 0.05). Conclusions Capsaicin can inhibit tumor growth and angiogenesis in Lewis lung cancer of mice which might be related to the down-regulation of HIF-1α and VEGF.