摘要
目的探讨复方苦参注射液(CKI)对乳腺癌(BC)模型大鼠肿瘤生长和转移的作用,以及对Hippo-YAP信号通路的调节机制。方法将BC细胞MDA-MB-231分为对照组(未处理组),Verteporfin(Hippo-YAP通路抑制剂)组,CKI低、中、高浓度组,采用CCK-8法检测MDA-MB-231细胞存活率;流式细胞仪检测MDA-MB-231细胞凋亡率;Transwell检测MDA-MB-231细胞的迁移能力。构建BC大鼠模型分为对照组,模型组,阳性组(Hippo-YAP通路抑制剂-Verteporfin组),CKI低、中、高剂量组;测量大鼠肿瘤生长情况;HE染色观察肿瘤发生肺转移后肺组织的病理学形态;Western blot检测肿瘤组织中YAP、p-YAP、E-cadherin、N-cadherin、Vimentin蛋白的表达。结果体外实验发现,与对照组相比,Verteporfin组和CKI不同浓度组细胞存活率和迁移能力降低,细胞凋亡率升高(P<0.05);体内实验显示,与对照组相比,模型组大鼠体内出现肿瘤组织块,肺组织中细胞排列不整齐,肺泡明显皱缩,且间隔增宽,组织异质性明显,YAP、N-cadherin、Vimentin蛋白表达升高,p-YAP、E-cadherin表达降低(P<0.05);与模型组相比,Verteporfin组和CKI各剂量组大鼠体内肿瘤组织减小,抑瘤率增加,肺组织中细胞排列有序,肺泡皱缩和异质性得到改善,YAP、N-cadherin、Vimentin蛋白表达降低,p-YAP、E-cadherin表达升高(P<0.05)。结论CKI可以通过抑制Hippo-YAP信号通路,来抑制BC模型大鼠肿瘤的生长和转移。
Objective To investigate the effects of Compound Kushen Injection(复方苦参注射液,CKI)on tumor growth and metastasis in breast cancer(BC)model rats,and the regulatory mechanism on Hippo-YAP signaling pathway.Methods BC cells MDA-MB-231 were divided into control group(untreated group),Verteporfin(Hippo-YAP pathway inhibitor)group,low,medium and high concentration CKI groups,the survival rate of MDA-MB-231 cells was detected by CCK-8 method;the apoptosis rate of MDA-MB-231 cells was detected by flow cytometry;Transwell was applied to detect the migration ability of MDA-MB-231 cells.BC rat models were divided into control group,model group,positive group(HippoYAP pathway inhibitor-Verteporfin group),low,medium and high dose CKI groups;the growth of tumor was measured;HE staining was applied to observe the pathological morphology of lung tissue after lung metastasis;Western blot was applied to detect the expression of YAP,p-YAP,E-cadherin,N-cadherin and Vimentin in tumor tissues.Results Compared with the control group,the cell survival rate and migration ability of Verteporfin group and CKI groups with different concentrations decreased,and the cell apoptosis rate increased(P<0.05);the in vivo experiment showed that compared with the control group,the model group rats had tumor tissue blocks,cells in the lung tissue were irregularly arranged,alveoli were obviously shrunk,and the spacing was widened,and the tissue heterogeneity was obvious,the expression of YAP,N-cadherin and Vimentin proteins increased,the expression of p-YAP and E-cadherin decreased(P<0.05);compared with the model group,the tumor tissue of the rats in the Verteporfin group and CKI groups decreased,the tumor inhibition rate increased,the cells in the lung tissue were arranged orderly,and the alveolar shrinkage and heterogeneity were improved,the expression of YAP,N-cadherin and Vimentin proteins decreased,the expression of p-YAP and E-cadherin increased(P<0.05).Conclusion CKI can inhibit tumor growth and metastasis in BC model rats by inhibiting Hippo-YAP signal pathway.
作者
吴海滨
马志强
张冠男
李帅
苗雅云
湛喜梅
王文胜
WU Haibin;MA Zhiqiang;ZHANG Guannan;LI Shuai;MIAO Yayun;ZHAN Ximei;WANG Wensheng(The First Affiliated Hospital of Henan University,Kaifeng 475100,Henan,China)
出处
《辽宁中医药大学学报》
CAS
2023年第11期72-76,共5页
Journal of Liaoning University of Traditional Chinese Medicine
基金
开封市科技发展计划项目(2203028)。
