断体地龙提取液对结肠炎相关性结肠癌COX-2/PGE_2/β-catenin信号通路的影响
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摘要
目的:观察断体地龙提取液对结肠炎相关性结肠癌小鼠COX-2/PGE_2/β-catenin信号通路的影响。方法:60只C57BL/6J雄性小鼠随机分为空白组、模型组、断体地龙提取液低、中、高剂量组和柳氮磺吡啶组。除空白组外,其余5组均采用氧化偶氮甲烷/葡聚糖硫酸钠法复制结肠炎相关性结肠癌模型。连续治疗15d后光镜下观察结肠组织病理学改变,并观察小鼠DAI评分、结肠器官重量及结肠组织成瘤率;Western-blot法检测结肠组织中COX-2、PGE_2和β-catenin蛋白的表达。结果:断体地龙提取液能够显著改善CACC小鼠结肠黏膜的病理学形态,降低小鼠DAI评分及结肠质量,减少结肠中瘤体的形成,明显优于模型组(P<0.05);断体地龙提取液能够显著降低结肠组织中COX-2、PGE_2、β-catenin蛋白的表达,与模型组比较明显优于模型组(P<0.05)。结论:断体地龙提取液能够通过抑制COX-2/PGE_2/β-catenin信号通路的激活,从而抑制结肠炎诱发的结肠癌的发生。
Objective:To observe the effect of amputated lumbricus extract on COX-2/PGE_2/β-catenin signaling pathway of the mice with colitis-associated colon cancer.Methods:Sixty male mice(C57 BL/6 J) were randomly divided into the control group,model group,and amputated lumbricus extract low,medium and high dose groups and sulfasalazine group.Mice were treated with oxidized azobenzene and dextran sulfate to replicate colitis-associated colon cancer model except the control group.After 15 days of continuous treatment,the pathological changes of colonic tissue were observed by optical microscope and the DAI score,the weight of colon organ and the tumor formation rate of colon were observed.Meantime,the expression of COX-2,PGE_2 and β-catenin protein in colonic tissue was detected by Western-blot expression.Results:The pathological morphology of colonic mucosa was significantly improved,the DAI score and the weight of colon organ were decreased,and the formation of tumor in colon were reduced with amputated lumbricus extract.And which were significantly better than those in the model group(P<0.05).Besides,the expression of COX-2,PGE_2 and β-catenin in colon tissue could be downregulated with amputated lumbricus extract,which were also significantly better than those in model group(P<0.05).Conclusion:Amputated lumbricus extract can inhibit the colitis-induced colorectal cancer by inhibiting the activation of COX-2/PGE_2/β-catenin signaling pathway.
Objective:To observe the effect of amputated lumbricus extract on COX-2/PGE_2/β-catenin signaling pathway of the mice with colitis-associated colon cancer.Methods:Sixty male mice(C57 BL/6 J) were randomly divided into the control group,model group,and amputated lumbricus extract low,medium and high dose groups and sulfasalazine group.Mice were treated with oxidized azobenzene and dextran sulfate to replicate colitis-associated colon cancer model except the control group.After 15 days of continuous treatment,the pathological changes of colonic tissue were observed by optical microscope and the DAI score,the weight of colon organ and the tumor formation rate of colon were observed.Meantime,the expression of COX-2,PGE_2 and β-catenin protein in colonic tissue was detected by Western-blot expression.Results:The pathological morphology of colonic mucosa was significantly improved,the DAI score and the weight of colon organ were decreased,and the formation of tumor in colon were reduced with amputated lumbricus extract.And which were significantly better than those in the model group(P<0.05).Besides,the expression of COX-2,PGE_2 and β-catenin in colon tissue could be downregulated with amputated lumbricus extract,which were also significantly better than those in model group(P<0.05).Conclusion:Amputated lumbricus extract can inhibit the colitis-induced colorectal cancer by inhibiting the activation of COX-2/PGE_2/β-catenin signaling pathway.
引文
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[2]王域,梁月培,肖瑶.大肠癌发病分子机制研究进展[J].中国肿瘤临床与康复,2017,24(8):1023-1024.
[3]殷媛,王成,戴欣,等.肠炎和肠炎相关结直肠癌mi RNA表达检测及生物信息学分析[J].中国癌症杂志,2016,26(11):916-921.
[4]张瑞,朱娜,马静,等.一种溃疡性结肠炎相关性结肠癌小鼠模型的建立[J].山西医科大学学报,2016,47(8):720-723.
[5]Lindsey N.Jackson,Yuning Zhou,Suimin Qiu,et al.Alternative Medicine Products as a Novel Treatment Strategy for Inflammatory Bowel Disease[J].American Journal of Chinese Medicine,2008,36(5):953-965.
[6]吴柯,何百成,周岐新.黄连总碱对大鼠结肠癌的化学预防作用[J].中国实验方剂学杂志,2011,17(8):200-203.
[7]曹阳,赵丹玉,柴纪严,等.四神丸对小鼠结肠炎性病变后诱发结肠癌化学预防作用研究[J].辽宁中医药大学学报,2012,14(11):127-129.
[8]张晓贤,孙剑经,刘华,等.NS-398对人结肠癌HCT-8细胞增殖、凋亡的影响及机制[J].山东医药,2016,56(25):8-12.
[9]聂芳,赵贤元,余跃天,等.PPARα/COX-2/PGE2通路在人结肠癌耐药细胞中的作用研究[J].现代消化及介入诊疗,2015,20(6):586-591.
[10]刘宣,王炎,隋华,等.健脾解毒方通过COX-2-Wnt/β-catenin信号通路抑制裸鼠人结肠癌血管新生[J].中华中医药杂志,2013,28(5):1276-1280.
[11]胡海聪,李翠芬,张硕峰,等.断体地龙再生期提取液对成纤维细胞增生作用的研究[J].中华中医药学刊,2013(5):1126-1128.