地龙提取液对结肠炎相关性结肠癌Wnt/β-catenin信号通路的影响

Effect of Earthworm Extract on Wnt/β-catenin signaling pathway in colitis-associated colorectal cancer

[目的]探讨地龙提取液对结肠炎相关性结肠癌疗效及其作用机制。[方法]小鼠随机分为空白组、模型组、地龙提取液(低、中、高剂量组)和美沙拉嗪组,并采用AOM/DSS法复制结肠炎相关性结肠癌癌前病变动物模型。治疗结束后分别测量各组小鼠胸腺、脾脏及结肠的质量,并光镜下观察结肠组织病理学改变,免疫印迹法检测结肠组织中Wnt/β-catenin信号通路中相关蛋白的表达。[结果]地龙提取液能够显著增加小鼠胸腺的质量和结肠长度(P<0.05),减少脾脏和结肠质量(P<0.05),降低AOM/DSS诱导小鼠的成瘤率(P<0.05),改善CAC小鼠结肠组织的病理学形态;此外,地龙提取液能够显著减少CAC小鼠结肠组织中Wnt3a、phospho-GSK-3β、β-catenin、c-Myc、cyclin-D1蛋白表达(P<0.05),增加APC、Axin1、GSK-3β、phospho-β-catenin、Bcl-2蛋白的表达(P<0.05)。[结论]地龙提取液能够预防结肠炎后结肠癌的发生与发展,其作用机制是通过抑制Wnt/β-catenin信号通路的活化实现的。

[Objective]To observe the effect of Earthworm extract on colitis associated colon cancer mice and its mechanism.[Methods]72mice were randomly divided into the control group,model group,Earthworm extract low,medium,high dose group and Mesalazine group,colitis associated colon cancer precancerous lesions model was duplicated by AOM/DSS method.After treatment,the weight of thymus,spleen and colon in each group were measured.The pathological changes of colon tissue were observed under light microscope,and the expression of related proteins in Wnt/β-catenin signaling pathway were detected by Western blot.[Results]The weight of thymus and colon length were increased significantly after treated with the Earthworm extract(P<0.05),while the weight of the spleen and colon were decreased significantly after treatment(P<0.05),and tumor formation rate was also reduced after treatment(P<0.05).Pathological morphology of colon tissue in CAC mice was improved in Earthworm extract low,medium,high dose group and Mesalazine group.In addition,Earthworm extract could significantly reduce the expression of Wnt3 a,phospho-GSK-3β,β-catenin,c-Myc,cyclin-D1proteins(P<0.05),and increase the expression of APC,Axin1,GSK-3β,phospho-β-catenin,Bcl-2proteins in colon tissue of mice in CAC(P<0.05).[Conclusion]Earthworm extract can prevent the occurrence and development of colitis associated colon cancer,and its mechanism is achieved by inhibiting the activation of Wnt/β-catenin signaling pathway.