摘要
目的探讨放射性^(125)I粒子对肝癌裸鼠皮下移植瘤微血管形成的影响及其机制。方法构建人肝癌Huh7细胞裸鼠皮下移植瘤模型,将12只裸鼠用随机数表法分为观察组和对照组,每组6只。观察组移植瘤植入一枚活度为2.96×10^(7)Bq粒子,对照组植入一枚活度为0的空粒子。每4天测量1次移植瘤体积,记录肿瘤生长曲线。28 d后取下移植瘤,用免疫组织化学染色法检测CD31评估移植瘤微血管密度(MVD)。用免疫组织化学染色法检测血管内皮生长因子-A(VEGF-A)、缺氧诱导因子1α(HIF-1α)蛋白表达,并做半定量分析。用实时荧光定量聚合酶链反应(RT-PCR)检测VEGF-A、HIF-1αmRNA的表达。结果观察组移植瘤的生长速度较对照组缓慢,粒子植入后12 d两组肿瘤体积差异有统计学意义(t=3.167,P<0.05),随着观察时间延长,两组肿瘤体积差距加大,在28 d时两组肿瘤体积分别为(963.61±89.56)mm^(3)和(602.10±75.98)mm^(3)(t=7.122,P<0.05)。两组移植瘤组织中CD31均有表达,观察组的MVD较对照组少,差异有统计学意义(t=6.360,P<0.05)。观察组VEGF-A、HIF-1αmRNA及蛋白的表达水平均低于对照组,差异均有统计学意义(t=10.480、6.414、10.890、12.250,P<0.05)。结论放射性^(125)I粒子通过降低肿瘤微血管密度抑制肝癌移植瘤的生长,其机制可能与VEGF-A、HIF-1α的mRNA及蛋白表达减少有关。
Objective To investigate the effect of radioactive ^(125)I seed on angiogenesis of subcutaneously transplanted hepatocellular carcinoma in nude mice and underlying mechanism.Methods The subcutaneous transplanted tumor model of human hepatocellular carcinoma Huh7 cells was established in nude mice.Twelve nude mice were randomly divided into observation group and control group with 6 mice in each group.The ^(125)I seed with activity of 2.96×10^(7)Bq was implanted into the transplanted tumor of observation group and another with 0 Bq as control group,respectively.The volume of the transplanted tumor was measured every 4 d and the growth curve of the tumor was recorded.The microvessel density(MVD)of the transplanted tumor was evaluated by immunohistochemical detection of CD31.VEGF-A and HIF-1αprotein and mRNA were detected by immunohistochemistry and RT-PCR,respectively.Results The growth rate of tumor in the observation group was slower than that in the control group,and the difference of tumor volume between two groups at 12 d after ^(125)I seed implantation was significantly different(t=3.167,P<0.05).At 28 d after transplantation,the tumor volumes of control and observation group approached to(963.61±89.56)mm^(3)and(602.10±75.98)mm^(3),respectively.The MVD of the observation group was significantly lower than that of the control group(t=6.361,P<0.05).The relative expression of VEGF-A and HIF-1αmRNA in the observation group was significantly lower than that in the control group(t=10.480,6.414,P<0.05).Protein expression levels of VEGF-A and HIF-1αin the observation group were lower than those in the control group(t=10.890,12.250,P<0.05).Conclusions Radioactive ^(125)I seed can inhibit the growth of HCC xenografts by reducing tumor microvessels,which may be related to the decrease of VEGF-A and HIF-1αexpression.
作者
杨崇双
刘平平
黄学全
肖云华
刘鹤男
李良山
李廷源
Yang Chongshuang;Liu Pingping;Huang Xuequan;Xiao Yunhua;Liu Henan;Li Liangshan;Li Tingyuan(Department of Nuclear Medicine,the First Affiliated Hospital of Army Medical University,Chongqing 400038,China)
出处
《中华放射医学与防护杂志》
CAS
CSCD
北大核心
2021年第11期808-812,共5页
Chinese Journal of Radiological Medicine and Protection
基金
重庆市社会事业与民生保障科技创新专项(cstc-2016shms-ztzx0045)。
