白藜芦醇调控HIF-1α/VEGF信号通路抑制肝癌血管生成的机制  

Resveratrol inhibits liver cancer angiogenesis by regulating HIF-1α/VEGF signaling pathway

作　　者：毛志方[1] 宋美娇 沈庆林 MAO Zhi-fang;SONG Mei-jiao;SHEN Qing-lin(Department of Oncology,Jiangxi Provincial People′s Hospital,the First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,Jiangxi,China)

机构地区：[1]江西省人民医院(南昌医学院第一附属医院)肿瘤科,江西南昌330006

出　　处：《广东医学》2025年第2期161-166,共6页Guangdong Medical Journal

基　　金：江西省中医药管理局科技计划项目(2021A370)。

摘　　要：目的探究白藜芦醇通过调节缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对肝癌血管生成的影响及机制。方法构建肝癌高、低转移潜能细胞系的小鼠模型,并配备低、中、高浓度的白藜芦醇腹腔注射小鼠模型;用环磷酰胺腹腔注射小鼠作对照组;用生理盐水腹腔注射小鼠作空白对照组;用RT-PCR法及Western blot法分别检测白藜芦醇组、环磷酰胺组、空白对照组干预14 d后各组小鼠肿瘤组织中HIF-1α、VEGF的mRNA及蛋白质水平,免疫组织化学染色评估肿瘤组织中血小板-内皮细胞黏附分子(CD31)表达水平,计算肿瘤组织中微血管密度(MVD)。结果白藜芦醇对肝癌荷瘤小鼠肿瘤生长具有显著的抑制作用,HCCLM3移植瘤组环磷酰胺及白藜芦醇低、中、高剂量抑瘤率分别为62.36%、23.62%、37.18%、48.54%;MHCC97-L移植瘤组环磷酰胺及白藜芦醇低、中、高剂量抑瘤率分别为68.47%、29.52%、43.58%、56.29%;白藜芦醇各给药剂量组可不同程度下调肝癌荷瘤小鼠肿瘤组织HIF-1α及VEGF mRNAs及蛋白表达(P<0.01),减少肿瘤组织中MVD(P<0.01)。结论白藜芦醇可抑制肝癌荷瘤小鼠肿瘤生长,其作用机制可能是通过减少肿瘤组织中HIF-1α及VEGF表达,抑制肿瘤血管生成。Objective To investigate the effect and mechanism of resveratrol on angiogenesis in liver cancer by regulating the hypoxia inducible factor 1 alpha(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods Mouse models of high-and low-metastatic potential HCC cell lines were established.The mice were treated with intraperitoneal injections of resveratrol at low,medium,and high doses.Cyclophosphamide was used as a positive control group,while normal saline was used for the blank control group.After 14 days of intervention,HIF-1αand VEGF mRNA and protein expression levels in tumor tissues were analyzed by RT-PCR and Western blot.Immunohistochemical staining was used to assess the expression of CD31(platelet-endothelial cell adhesion molecule)in tumor tissues,and microvessel density(MVD)was calculated.Results Resveratrol significantly inhibited tumor growth in tumor-bearing mice.In the HCCLM3 transplanted tumor group,the tumor inhibition rates for cyclophosphamide and low,medium,and high doses of resveratrol were 62.36%,23.62%,37.18%,and 48.54%,respectively.In the MHCC97-L transplanted tumor group,the tumor inhibition rates were 68.47%,29.52%,43.58%,and 56.29%,respectively.Resveratrol at all doses reduced the expression of HIF-1αand VEGF mRNA and protein in tumor tissues to varying degrees(P<0.01)and significantly decreased MVD in tumor tissues(P<0.01).Conclusion Resveratrol inhibits tumor growth in HCC-bearing mice.Its mechanism may involve downregulation of HIF-1αand VEGF expression in tumor tissues,thereby suppressing tumor angiogenesis.

关 键 词：白藜芦醇 肝癌 血管生成 缺氧诱导因子-1α/血管内皮生长因子信号通路 

分 类 号：R735.7[医药卫生—肿瘤] R73-36[医药卫生—临床医学]