首页|扶正抑瘤方通过Wnt/β-catenin通路调节结肠癌大鼠肿瘤增殖、迁移、侵袭、凋亡的研究

扶正抑瘤方通过Wnt/β-catenin通路调节结肠癌大鼠肿瘤增殖、迁移、侵袭、凋亡的研究

Study of Fuzheng Yiliu Prescription in Regulating Tumor Proliferation,Migration,Invasion,and Apoptosis in Rats with Colon Cancer via Wnt/β-catenin Pathway

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目的:探究扶正抑瘤方调节结肠癌(Colon Cancer,CC)大鼠肿瘤增殖、迁移、侵袭及凋亡作用效果及其作用机制.方法:研究对象选取SPF 级雄性大鼠 36 只,随机分为对照组、模型组及低剂量组、高剂量组,每组 9 只,对照组不进行干预,模型组及低、高剂量组建立CC大鼠模型.建模成功后,模型组给予生理盐水灌胃,低、高剂量组分别给予低剂量及高剂量扶正抑瘤方灌胃.比较各组肿瘤变化、病理学变化、肿瘤侵袭、迁移相关指标及肿瘤细胞凋亡相关蛋白表达.结果:模型组呈现结肠长度缩短并伴有大量结肠肿瘤形成,低剂量组结肠长度较模型组增加,肿瘤减少,高剂量组肿瘤负荷进一步降低;HE染色结果显示模型组表现出明显肿瘤病变,低剂量组结肠肿瘤病变缓解,高剂量组在其基础上进一步改善;低剂量组、高剂量组大鼠病灶组织血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、肝癌衍生生长因子(HDGF)、单核细胞趋化蛋白-1(MCP-1)、转化生长因子-β(TGF-β)、基质金属蛋白酶抑制剂-1(TIMP-1)水平、基质金属蛋白酶 9(MMP9)、肿瘤坏死因子受体相关蛋白(TRAP1)mRNA、糖原合酶激酶 3β(GSK3β)、周期素D1、C-myc癌基因蛋白、凋亡抑制基因Bcl-2 蛋白(Bcl-2)、β-连环蛋白(β-catenin)、微血管密度低于模型组(P<0.05),且高剂量组低于低剂量组(P<0.05);低剂量组、高剂量组大鼠钙黏蛋白(E-cadherin)、KRUPPEL样因子 4(KLF4)高于模型组,且高剂量组高于低剂量组(P<0.05);模型组Bcl-2、Bcl2 关联X蛋白(Bax)表达较对照组升高,低剂量组、高剂量组与模型组比较,Bcl-2 表达降低,Bax表达升高,且呈现剂量依赖性变化.结论:扶正抑瘤方能有效抑制CC大鼠肿瘤增殖、迁移、侵袭,提高大鼠肿瘤细胞凋亡相关蛋白表达,促进肿瘤细胞凋亡,其作用机制可能为通过抑制Wnt/β-catenin信号通路激活从而调控其下游因子.
Objective:To investigate the effectiveness and mechanism of Fuzheng Yiliu Prescription in regulating tumor prolifera-tion,migration,invasion,and apoptosis in rats with colon cancer(CC).Methods:Thirty-six SPF-grade male rats were selected and ran-domly divided into a control group,a model group,and a low-dose treatment group and a high-dose treatment group,with 9 rats in each group.The control group received no intervention.Rats in the model group and the treatment groups underwent the establishment of a CC model.The model group was then gavaged with saline,while the treatment groups were gavaged with low-dose and high-dose Fuzheng Yi-liu Prescription,respectively.Comparisons were made among the groups in terms of tumor changes,pathological changes,tumor invasion and migration-related indicators,and the expression of tumor cell apoptosis-related proteins.Results:The model group exhibited short-ened colon length accompanied by the formation of numerous colon tumors.In the low-dose group,there was an increase in colon length and a reduction in tumors,while in the high-dose group,the tumor burden was further reduced.HE staining revealed obvious tumor pa-thology in the model group,which was mitigated in the low-dose group and further improved in the high-dose group.Compared to the model group,the levels of vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),hepatoma-derived growth factor(HDGF),monocyte chemotactic protein-1(MCP-1),transforming growth factor-β(TGF-β),tissue inhibitor of metalloproteinase-1(TIMP-1),matrix metalloproteinase 9(MMP9),tumor necrosis factor receptor-associated protein 1(TRAP1)mRNA,glycogen synthase kinase 3β(GSK3β),cyclin D1,C-myc oncogene pro-tein,anti-apoptotic gene protein Bcl-2(Bcl-2),β-catenin,and microvascular density were lower in both the low-dose and high-dose groups,with the high-dose group showing even lower levels than the low-dose group(P<0.05).In the low-dose group and high-dose group,the E-cadherin and KRUPPEL-like factor 4(KLF4)in rats were higher than those in the model group,and the levels in the high-dose group were higher than those in the low-dose group(P<0.05).The model group had an increase in both Bcl-2 and Bcl-2-as-sociated X protein(Bax)expression.Compared with the model group,Bcl-2 expressiom decreased,and Bax expression increased in both the low-dose and high-dose groups,and these changes were dose-dependent manner.Conclusion:Fuzheng Yiliu Prescription effectively inhibits tumor proliferation,migration,and invasion in CC rats,enhances the expression of tumor cell apoptosis-related proteins,and pro-motes tumor cell apoptosis.The mechanism of action may involve regulating downstream factors by inhibiting the activation of the Wnt/β-catenin signaling pathway.

Fuzheng Yiliu PrescriptionWnt/β-catenincolon cancerratstumor proliferationmigrationinvasionapoptosis

胡嘉芮、渠少博、何晓华、刘戴维、王永霞、樊捷婷、武晓媛、李占林

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河北北方学院附属第一医院,河北张家口 075000

扶正抑瘤方 Wnt/β-catenin 结肠癌 大鼠 肿瘤增殖 迁移 侵袭 凋亡

2024

河北中医药学报
河北医科大学

河北中医药学报

CSTPCD
影响因子:0.865
ISSN:1007-5615
年,卷(期):2024.39(6)