基于影响肿瘤间质血管生成探讨枸杞多糖抗小鼠结直肠癌作用及机制

To Discuss the Effect and Mechanism of LBP on Colorectal Cancer in Mice Based on the Induction of Tumor Interstitial Vascular

摘要: 目的：观察枸杞多糖(Lycium barbarum polysaccharide, LBP)对小鼠结直肠癌皮下移植瘤生长的抑制作用，并探讨其作用的可能机制。方法：建立CT26小鼠结直肠癌皮下移植瘤模型，LBP给药12天，观察小鼠状态，测量移植瘤长短径绘制肿瘤生长曲线；肿瘤组织切片免疫组织化学方法检测CD31蛋白表达，观察肿瘤间质血管密度改变；大鼠动脉环实验观察LBP对血管形成的影响。体外实验RT-PCR检测LBP对血管生成抑制因子1 (BAI1)表达的影响。结果：肿瘤生长曲线发现LBP可抑制小鼠结直肠癌皮下移植瘤的生长，LBP给药组小鼠肿瘤体质量为0.31 ± 0.04 g明显小于对照组0.63 ± 0.06 g (P < 0.05)，CD31染色显示LBP给药组肿瘤间质微血管密度为31.6 ± 2.45，小于肿瘤模型组42.3 ± 3.28，差异具统计学意义(P < 0.05)；同时发现LBP对大鼠动脉环血管形成具有明显抑制作用，且呈浓度依赖性；RT-PCR检测发现LBP可上调BAI1 mRNA表达。结论：LBP具有抗小鼠结直肠癌肿瘤生长的作用，其机制可能与抑制肿瘤微血管形成、上调BAI1表达有关，其具体的作用机制有待进一步探究。

Abstract: Objective: To investigate the effect and mechanism of Lycium barbarum polysaccharides (LBP) on the growth and angiogenesis of mice with colorectal cancer. Methods: Firstly, we observed LBP administration inhibition effect of tumor growth and drew the tumor growth curve based on the CT26 colorectal cancer mouse model we built. Then, CD31 expression of tumor tissue sections, detected by immunohistochemical, was to measure the tumor interstitial microvascular density. Secondly, rat aortic ring experiment was to confirm the effect of LBP on angiogenesis. In vitro RT-PCR was used to detect the effect of LBP on the expression of brain specific angiogenesis inhibitor 1 (BAI1). Result: The tumor growth curve found that LBP could inhibit the growth of mouse model of colorectal cancer tumor, the tumor weight of LBP group was (0.31 ± 0.04) g which was significantly less than that of the control group (0.63 ± 0.06) g (P < 0.05), CD31 staining showed that the tumor interstitial microvascular density (42.3 ± 3.28) of control group was more than that of LBP group (31.6 ± 2.45) (P < 0.05; LBP); the concentration of microvascular of LBP was less than that of control group, the obvious inhibitory angiogenesis effect was observed on rat aortic ring, which was related with the LBP concentration. In vitro LBP could increase the expression of BAI1 mRNA (brain tissue specific angiogenesis inhibitor 1). Conclusion: The inhibitory effect of LBP on the growth of colorectal cancer in mice may be related to the inhibition of angiogenesis and upregulation of BAI1 expression, but the specific mechanism needs further clarification.