枸杞多糖对小鼠结直肠癌肿瘤生长的抑制作用及对血管形成机制的影响

Lycium Barbarum Polysaccharides Has Effect on the Inhibiton of Growth of Colorectal Cancer and the Mechanism of Angiogenesis in Mice

目的:探讨枸杞多糖(LBP)对小鼠结直肠癌肿瘤生长及血管形成机制的影响。方法:建立小鼠CT26结直肠癌肿瘤模型,LBP给药观察对模型小鼠肿瘤生长的抑制作用,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表达,观察肿瘤间质血管密度;大鼠动脉环实验观察LBP对血管形成的影响。体外实验QPCR检测LBP对脑组织特异性血管生成抑制因子1(BAI1)表达的影响,同时检测LBP对结直肠癌细胞株(CT26)及人真皮微血管内皮细胞株(HDMEC)增殖的影响。结果:LBP用药组CT26结直肠癌小鼠肿瘤重量为(0.31±0.04)g小于对照组(0.63±0.06)g(P<0.05);绘制肿瘤生长体积曲线,发现LBP可抑制小鼠肿瘤的生长(P<0.05)。CD31染色显示LBP用药组小鼠肿瘤间质血管密度小于模型组(P<0.05)。LBP对大鼠动脉环血管形成具有明显抑制作用,且与浓度有关。体外实验发现,与对照组比较,LBP 500μg/m L及1 000μg/m L处理HDMEC后,BAI1表达上调(P<0.01);LBP药物浓度设定在0~1 000μg/m L之间,随着浓度的增加,LBP对小鼠结直肠癌CT26细胞及HDMEC细胞增殖均无明显的影响。结论:LBP对小鼠结直肠癌生长的抑制作用可能与抑制血管形成、上调BAI1表达有关,但具体的作用机制有待进一步阐明。

Objective：To discuss the effect of lycium barbarum polysaccharides（LBP） on the inhibiton of growth of colorectal cancer（CRC） and the mechanism of angiogenesis in mice with colorectal neoplasms. Methods： Established CT26 colorectal cancer tumor model of mice,observed the inhibiton of growth of tumor in model mice with LBP administration,drew a tumor growth curve,made tumor tissue sections, detected CD31 expression by applying immunohistochemical method, and observed tumor interstitial vascular density. Arterial rings experiments of rats were used to observe the effect of LBP on angiogenesis. In vitro QPCR was used to detect the effect of LBP on expression of brain tissue-specific angiogenesis inhibitor 1（BAI1） and the proliferation of CT26（colorectal cancer cell line） and microvascular endothelial cells of human skin（HDMEC）. Results： The weight of colorectal neoplasms in mice in the medication group of LBP was（0.31±0.04）g,being lower than that of（0.63±0.06）g in the control group（P〈0.05）. LBP was found able to inhibit the growth of mouse tumor by means of drawing the tumor growth volume curve（P〈0.05）. CD31 staining showed that the tumor interstitial vascular density was lower in the the medication group of LBP than that in the model group（P〈0.05）. LBP has a significant inhibitory effect on angiogenesis of arterial ring in rats, and it is related to the concentration. In vitro experiments showed that,compared with the control group,BAI1 expression was up-regulated after HDMEC was treated with LBP 500 μg/m L and 1 000μg/m L（P〈0.01）. LBP drug concentration was set between 0 and 1 000 μg/m L,and as the concentration increased,LBP had no significant effect on the proliferation of CT26 cells and HDMEC cells in colorectal cancer in mice. Conclusion：The inhibitory effect of LBP on the growth of colorectal cancer may be related to inhibiting angiogenesis and up-regulating BAI1 expression, but the specific mechanism remains to be further illustrated.