西黄丸调控HIF-1α抑制胃癌MGC-803细胞荷瘤裸鼠血管生成拟态的机制研究  

Mechanisms of Xihuang Pill on inhibiting vasculogenic mimicry of gastric cancer MGC-803 cells in tumor-bearing mice by regulating HIF-1α

作　　者：郭秋均[1] 高业博 魏华民[3] 刘瑞[1] 花宝金[1] 李丛煌[1] GUO Qiu-jun;GAO Ye-bo;WEI Hua-min;LIU Rui;HUA Bao-jin;LI Cong-huang(Department of Ontology,Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Department of Ontology,Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100012,China;Beijing Friendship Hospital Affiliated to the Capital Medical University,Beijing 100050,China)

机构地区：[1]中国中医科学院广安门医院肿瘤科,北京100053 [2]中国中医科学院望京医院肿瘤科,北京100102 [3]首都医科大学附属北京友谊医院,北京100050

出　　处：《北京中医药》2021年第9期940-945,共6页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(81202656,81904196);中国科协青年人才托举计划项目(YESS20180272)。

摘　　要：目的探讨西黄丸通过调控HIF-1α对胃癌MGC-803细胞荷瘤裸鼠血管生成拟态的影响。方法BALB/c裸鼠荷瘤造模成功后按数字表法随机分为空白组、西黄丸组、2-甲氧基雌二醇(2-ME)组、西黄丸+2-ME结合组4组,各6只,分别予相应措施干预14 d,测量计算各组裸鼠肿瘤体积,RT-qPCR检测血管内皮钙黏附分子(VE-Cadherin)、肝配蛋白A型受体2(EphA2)、基质金属蛋白酶2(MMP-2)、乏氧因子1α(HIF-1α)的mRNA表达,免疫组化法检测VE-Cadherin、EphA2、p-EphA2、MMP-2蛋白表达,Western-blot法检测HIF-1α蛋白表达。结果西黄丸可以抑制胃癌细胞的增殖,降低胃癌肿瘤体积和质量(P<0.05),减少胃癌组织血管生成拟态形成数量,降低VE-Cadherin、MMP-2的mRNA表达(P<0.01)和蛋白表达(P<0.05),抑制EphA2蛋白磷酸化(P<0.05),降低乏氧关键因子HIF-1α蛋白及mRNA表达(P<0.01)。结论西黄丸可通过调控HIF-1α抑制胃癌MGC803细胞血管生成拟态形成。Objective To investigate the effect of Xihuang Pill on vasculogenic mimicry(VM) of gastric cancer MGC-803 cells in tumor-bearing mice by regulating HIF-1α.Methods BALB/c nude mice were randomly divided into four groups by numerical table method after tumor bearing modeling: Blank control group, Xihuang Pill group, 2-ME group, Xihuang Pill+2-ME combination group, 6 mice in each group, and they were given corresponding intervention measures for 14 days respectively.Tumor volume of mice in each group was measured and calculated, mice were killed with their necks removed, and tumor tissues were collected from each group.The mRNA expressions of VE-cadherin, EphA2,MMP-2 and HIF-1α were detected by RT-qPCR,the protein expressions of VE-cadherin, EphA2,p-EPHA2 and MMP-2 were detected by immunohistochemistry, and the protein expression of HIF-1α was detected by Western-blot.Results Xihuang Pill could inhibit the proliferation of gastric cancer cells and decrease the volume and mass of gastric cancer cells(P<0.05),decrease the number of VM formation in gastric cancer tissues, decrease the mRNA expression of VE-cadherin and MMP-2(P<0.01) and protein expression(P<0.05),inhibit the phosphorylation of EPHA2(P<0.05),and reduce the expression of HIF-1α protein and mRNA,the key factor of hypoxia(P<0.01).Conclusion Xihuang Pill can inhibit the VM formation of gastric cancer MGC803 cells by regulating HIF-1α.

关 键 词：西黄丸 2-ME 胃癌 血管生成拟态 乏氧因子 裸鼠 

分 类 号：R285.5[医药卫生—中药学]