桂枝茯苓丸调节Shh/Gli1信号通路对乳腺癌细胞增殖、迁移和血管生成的影响  

Effects of Guizhi Fuling Wan on proliferation, migration and angiogenesis of breast cancer cellsby regulating Shh/Gli1 signaling pathway

作　　者：杨森焱 张志东 彭文 陈吉柏 薛治乾 YANG Senyan;ZHANG Zhidong;PENG Wen;CHEN Jibai;XUE Zhiqian(Department of Thoracic Surgery,Danzhou People’s Hospital,Danzhou,Hainan 571700,China;Department of Pathology,Danzhou People’s Hospital,Danzhou,Hainan 571700,China)

机构地区：[1]儋州市人民医院胸外科,海南儋州571700 [2]儋州市人民医院病理科,海南儋州571700

出　　处：《中国优生与遗传杂志》2024年第10期2032-2038,共7页Chinese Journal of Birth Health & Heredity

摘　　要：目的 探究桂枝茯苓丸(GFW)是否通过调节音猬因子(Shh)/胶质瘤相关癌基因1(Gli1)信号通路对乳腺癌细胞增殖、迁移和血管生成产生影响。方法 以MCF7细胞为研究对象,CCK-8实验检测不同浓度的GFW对MCF7细胞增殖的抑制情况;将MCF7细胞分为Control组、L-GFW组、M-GFW组、H-GFW组、PM组。其中L-GFW组、M-GFW组、H-GFW组分别为100、300、600μg/mL GFW处理,PM组在600μg/mL GFW处理基础上添加1μmol/L Shh/Gli1信号通路激活剂purmorphamine(PM);观察各组细胞的克隆细胞数、迁移以及血管生成情况,分析Shh、Gli1、上皮间质转化相关蛋白(E-cadherin、Vimentin、N-cadherin)以及表皮生长因子受体蛋白(EGFR)的表达情况;构建乳腺癌小鼠模型,随机分为对照组(喂等量的生理盐水)、GFW组(290 mg/kg GFW喂养),麻醉处死,观察肿瘤质量、体积变化,免疫组化法检测Shh、Gli1蛋白的阳性表达率。结果 L-GFW组、M-GFW组、H-GFW组克隆、迁移细胞数、管腔形成数以及N-cadherin、Vimentin、Shh、Gli1、EGFR的蛋白表达低于Control组,E-cadherin蛋白表达高于Control组(P<0.05);激活剂处理则逆转上述表达。GFW组移植瘤质量、体积、Shh、Gli1的阳性表达率均低于对照组(P<0.05)。结论 GFW能抑制乳腺癌细胞的增殖、迁移以及血管生成,可能是通过抑制Shh/Gli1信号通路实现的。Objective To investigate whether Guizhi Fuling Wan(GFW)can affect the proliferation,migration and angiogenesis of breast cancer cells by regulating the sonic hedgehog(Shh)/glioma associated oncogene 1(Gli1)signaling pathway.Methods MCF7 cells were used as the research object,the CCK-8 experiment was applied to detect the inhibitory effect of different concentrations of GFW on MCF7 cell proliferation.MCF7 cells were divided into Control group,L-GFW group,M-GFW group,H-GFW group and PM group.The L-GFW group,M-GFW group,and H-GFW group were treated with 100,300,and 600μg/mL GFW,respectively.In PM group,1μmol/L Shh/Gli1 signaling pathway activator purmorphamine(PM)was added on the basis of 600μg/mL GFW treatment.The number of clones,migration,and angiogenesis of cells in each group were observed.The expression of Shh,Gli1,epithelial mesenchymal transition related proteins(E-cadherin,Vimentin,N-cadherin),and epidermal growth factor receptor protein(EGFR)was analyzed.The breast cancer mouse model was constructed and randomly divided into the Control group(fed with the same amount of normal saline)and the GFW group(fed with 290 mg/kg GFW).The mice were anesthetized and sacrificed to observe the changes of swelling mass and volume.The positive expression rate of Shh and Gli1 protein was detected by immunohistochemical method.Results The number of cloned and migrating cells,number of lumen formation,and protein expression of N-cadherin,Vimentin,Shh,Gli1,and EGFR in the L-GFW,M-GFW,and H-GFW groups were lower than those in the Control group,while the protein expression of E-cadherin was higher than that in the Control group(P<0.05).Activator treatment reversed the above expression.The quality and volume of transplanted tumors,and the positive expression rates of Shh and Gli1 in the GFW group were lower than those in the Control group(P<0.05).Conclusion GFW can inhibit the proliferation,migration and angiogenesis of breast cancer cells,which may be achieved by inhibiting Shh/Gli1 signaling pathway.

关 键 词：桂枝茯苓丸 音猬因子/胶质瘤相关癌基因1 乳腺癌 增殖 血管生成 

分 类 号：R285[医药卫生—中药学]