17-DMAG对PD-1人源化小鼠肝癌移植瘤的抑制作用
Inhibitory effect of 17-DMAG on PD-1 humanized mouse liver cancer transplantation tumor
李晓娟 1修叶 2李兴杰 1孙岩峰 3李瑞生1
作者信息
- 1. 中国人民解放军总医院第五医学中心感染病医学部研究所,北京 100039
- 2. 中国人民解放军总医院第五医学中心肝病医学部研究所,北京 100039
- 3. 中国人民解放军总医院第三医学中心儿科,北京 100039
- 折叠
摘要
目的 探讨17-二甲基胺乙基-17-去甲氧基格尔德霉素(17-DMAG)对PD-1人源化小鼠人肝癌移植肿瘤生长的抑制作用.方法 选取30只PD-1人源化小鼠,将HepG2细胞悬液注射于小鼠右侧腹股沟皮下组织,构建人肝癌移植瘤模型;将荷瘤人源化小鼠随机分为3组(每组10只):①模型组(注射生理盐水10 mg/kg);②17-DMAG组(按25 mg/kg腹腔注射17-DMAG,3次/周);③顺铂组(腹腔注射20 mg/kg,2次/周),实验持续4周.注射结束后测量人源化小鼠移植瘤的长、短径计算体积,测量肿瘤质量计算抑瘤率,同时采用免疫组化方法检测肿瘤组织中CD31(以阳性细胞数计算肿瘤微血管密度(MVD))及血管内皮生长因子(VEGF)的表达.结果 17-DMAG 组和顺铂组的肿瘤体积和质量均较模型组显著减小(P＜0.05),17-DMAG组的抑瘤率略高于顺铂组,但17-DMAG组和顺铂组肿瘤质量和体积以及抑瘤率均不存在显著性差异.17-DMAG组和顺铂组MVD标记微血管数量及VEGF表达均低于模型组(P＜0.05),且17-DMAG组又低于顺铂组(P＜0.05).结论 17-DMAG可显著降低肝癌移植瘤中VEGF的表达,抑制新生血管在肿瘤中发生发展,从而对人源化小鼠肝癌移植瘤发挥抑制作用.
Abstract
Objective To explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumors.Methods 30 PD-1 humanized mice were selected,and a human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region to construct a human liver cancer transplant tumor model.Tumor-bearing humanized mice were randomly divided into three groups(10 mice per group):① model group(injected with 10 mg/kg of physiological saline),②17-DMAG group(intraperitoneal injection of 17-DMAG at 25 mg/kg,3 times/week),and③cisplatin group(intraperitoneal injection of 20 mg/kg,2 times per week).The experiment lasted for 4 weeks.After injection,the length and shortest diameter of humanized mouse transplanted tumors were measured to calculate the volume,and tumor mass was measured to calculate the tumor inhibition rate.At the same time,immunohistochemical method were used to detect the expression of CD31(tumor microvessel density,MVD)and vascular endothelial growth factor(VEGF)in tumor tissue.Results The tumor volume and mass of the 17-DMAG group and cisplatin group were significantly reduced compared to those of the model group(P＜0.05),and the tumor inhibition rate of the 17-DMAG group was slightly higher than that of the cisplatin group.However,there were no significant differences in tumor mass,volume,and tumor inhibition rate between the 17-DMAG group and cisplatin group.The number of MVD-labeled microvessels and level of VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group(P＜0.05),and those of the 17-DMAG group were also lower than those in the cisplatin group(P＜0.05).Conclusions 17-DMAG can inhibit the growth of humanized mouse liver cancer xenografts by reducing the expression of VEGF in liver cancer xenograft tissue,thereby inhibiting the generation of tumor neovascularization.
关键词
PD-1人源化小鼠/17-DMAG/肝癌/微血管密度/血管内皮细胞生长因子Key words
PD-1 humanized mice/17-DMAG/liver cancer/microvessel density/vascular endothelial growth factor引用本文复制引用
基金项目
军队实验动物专项基金面上项目(SYDW[2020]05号)
出版年
2024
国家科技期刊平台
NSTL
万方数据