阳和化岩汤对HER-2高表达型裸鼠荷瘤模型微淋巴管生成及PI3K/Akt交互调控通路的影响  

Effects of Yanghe Huanyan Decoction (阳和化岩汤) on the Microlymphangiogenesis and the Interaction Regulatory Pathway of PI3K/Akt in HER-2-Overexpressing Nude Mice

作　　者：刘晓菲 李静蔚[2] 孙庆颖 李湘奇[3] 张洋 王楠 LIU Xiaofei;LI Jingwei;SUN Qingying;LI Xiangqi;ZHANG Yang;WANG Nan(First Clinical College,Shandong University of Traditional Chinese Medicine,Jinan 250335;Affiliated Hospital of Shandong University of Traditional Chinese Medicine;Affiliated Hospital of Taishan Medical College;School of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine)

机构地区：[1]山东中医药大学第一临床学院 [2]山东中医药大学附属医院 [3]泰山医学院附属医院 [4]山东中医药大学中医学院

出　　处：《中医杂志》2019年第1期51-56,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81403408;81473687;81573989);山东省自然科学基金(ZRZ011HL065);山东省中医药科技发展计划(2013-ZDZK-024);山东省高等学校科技计划(J11LF53)

摘　　要：目的探讨阳和化岩汤治疗乳腺癌的可能作用机制。方法通过SK-BR-3细胞株接种建立Balb/c裸鼠荷瘤模型,将20只成瘤阳性的裸鼠随机分为模型组、中药组、西药组、中西药组,每组5只。模型组每天灌胃0. 4 ml生理盐水;中药组用阳和化岩汤18 g/(kg·d)灌胃;西药组给予曲妥珠单抗1 mg/kg,每周2次,腹腔注射;中西药组给予阳和化岩汤和曲妥珠单抗,用法同中药组和西药组。给药4周后观察各组淋巴结转移抑制率,检测肿瘤组织中磷脂酰肌醇-3羟基激酶(PI3K)、磷酸化丝氨酸/苏氨酸激酶(p-Akt)、血管内皮生长因子C (VEGFC)的表达,计数微淋巴管数量及VEGFC评分。结果各组裸鼠乳腺原位均有实体肿瘤生长,呈椭圆形或分叶状,原位移植乳腺癌模型裸鼠均有腋窝淋巴结转移。与模型组比较,各给药组淋巴结抑制率均上升,VEGFC评分及PI3K、p-Akt、VEGFC mRNA表达均降低,微淋巴管数量减少(P <0. 05或P <0. 01);与中药组、西药组比较,中西药组淋巴结抑制率明显升高,VEGFC评分及PI3K、p-Akt、VEGFC mRNA表达均降低,微淋巴管数量减少(P <0. 05或P <0. 01)。VEGFC评分与微淋巴管数量之间存在正相关关系(r=0. 894,P <0. 05)。结论阳和化岩汤能有效抑制HER-2高表达型裸鼠荷瘤模型微淋巴管生成,抑制血管生成调控通路及VEGFC表达,其机制可能与有效抑制PI3K/Akt交互调控通路活化有关。Objective To study the possible mechanism of Yanghe Huanyan Decoction(阳和化岩汤)in the treatment of breast cancer.Methods The tumor bearing model of Balb/c nude mice was established by inoculation of SK-BR-3 cell lines.The nude mice model of tumor was established and a total of 20 mice were randomly divided into model group,Chinese medicine(CM)group,trastuzumab group and trastuzumab+CM group,with 5 mice in each group.The model group was given 0.4 ml of normal saline every day;Yanghe Huayan Decoction 18 g/(kg·d)was used for gavage in CM group.Trastuzumab group was given trastuzumab 1 mg/kg,2 times a week,intraperitoneal injection;Yanghe Huanyan Decoction and trastuzumab were given to the trastuzumab+CM groups,and the usage was the same as that in the CM and trastuzumab groups.The inhibition rate of lymph node metastasis was observed after 4 weeks administration.The expression of key target proteins PI3 K,p-Akt and vascular endothelial growth factor C(VEGFC)in the PI3 K/Akt interaction pathway were detected by RT-PCR,and in tumor tissues was detected,and the number of lymphatic vessels and VEGFC score were counted.Results There were solid tumors in the mammary gland in each group,which were oval or lobulated,axillary lymph node metastasis was observed in nude mice with orthotopic breast cancer transplantation.Compared with the model group,the inhibition rate of lymph nodes increased in three treated group,VEGFC score and mRNA expression of PI3 K,p-Akt and VEGFC were decreased,and the number of microlymphatic vessels was decreased(P<0.05 or P<0.01).Compared with the CM group and the trastuzumab group,the lymph node inhibition rate was significantly increased in the trastuzumab+CM group,and VEGFC score,PI3 K,p-Akt and VEGFC mRNA expression were all decreased,and the number of microlymphatic vessels was reduced(P<0.05 or P<0.01).There was a positive correlation between VEGFC score and the number of microlymphatic vessels(r=0.894,P<0.05).Conclusion Yanghe Huanyan Decoction can effectively inhibit the formation o

关 键 词：乳腺癌 阳和化岩汤 曲妥珠单抗 PI3K/AKT通路 微淋巴管 血管内皮生长因子C 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]