雄黄外用对三阴性乳腺癌上皮间质转化的调控作用研究

Study on the Regulatory Effect of Realgar for External Use on Epithelial Mesenchymal Transformation in Triple Negative Breast Cancer

目的研究中药雄黄外用对三阴性乳腺癌上皮间质转化的作用及调控机制。方法采用人三阴性乳腺癌MDA-MB-231细胞构建裸鼠人乳腺癌移植瘤模型后,将裸鼠随机分为模型组、雄黄外用组、卡培他滨片组,干预6周后取材。通过HE染色、免疫组化、Western blot、qPCR等方法观察雄黄外用对乳腺癌肿瘤上皮间质转化的调控作用,同时对动物血常规,肝、肾功能指标进行检测。结果雄黄外用可使乳腺癌组织出现一定程度的坏死,抑瘤率为30.2%;与模型组比较,雄黄外用组裸鼠肝、肾功能及血常规检测等未见明显异常;肿瘤组织免疫组化结果提示,雄黄外用可增强上皮钙黏蛋白(E-cadherin)表达,降低波形蛋白(Vimentin)表达;Western blot和qPCR结果提示:与模型组比较,雄黄外用可上调肿瘤组织中E-cadherin表达,减弱Vimentin、Twist1、TGF-β1的表达,差异具有统计学意义(P<0.05)。结论雄黄外用可抑制人三阴性乳腺癌移植瘤在体生长,其机制与增强E-cadherin表达,降低Vimentin、Twist1、TGF-β1的表达,实现对乳腺癌上皮间质转化的调控相关。

OBJECTIVE To investigate the regulatory effect of realgar for external use on epithelial mesenchymal transformation in triple negative breast cancer.METHODS Human breast cancer nude mouse xenograft model was established by injecting MDA-MB-231 cells.The mice were randomly divided into model group,realgar group and capecitabine tablet group.Hematoxylin and eosin(HE),immunohistochemistry,Western blot and qPCR were used to observe the effect of realgar on epithelial-mesenchymal transition(EMT)of breast cancer.At the same time,the indexes of blood routine,liver and kidney function were detected.RESULTS External using realgar could induce necrosis of breast cancer tissue,the tumor inhibitory rate was 30.2%.Compared with the model group,the liver and kidney functions and blood routine tests of nude mice in realgar group were not significantly abnormal;The immunohistochemical results of tumor tissues suggested that realgar could enhance the expression of E-cadherin and reduce the expression of Vimentin;The results of Western blot and qPCR showed that realgar could enhance the expression of E-cadherin and reduce the expressions of Twist1 and TGF-β1 in tumor tissues(P<0.05).CONCLUSION External using realgar can inhibit the growth of triple negative breast cancer and regulate EMT by increasing the expression of E-cadherin and decreasing the expressions of Vimentin,Twist1 and TGF-β1.