17-DMAG对PD-1人源化小鼠肝癌移植瘤的抑制作用
作者:
作者单位:

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;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;3.中国人民解放军总医院第三医学中心儿科

基金项目:

] 军队实验动物专项基金面上项目(SYDW[2020]05号)[


Inhibitory effect of 17-DMAG on PD-1 humanized mouse liver cancer transplantation tumor
Author:
Affiliation:

1.Research Institute of Department of Infectious Diseases,Fifth Medical Center of Chinese PLA General Hospital;2.Research Institute of Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital;3.Pediatrics Department, Third Medical Center of Chinee PLA General Hospital

  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献 [17]
  • | |
  • 引证文献
  • | |
  • 文章评论
    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 可降低肝癌移植瘤组织中血管内皮细胞生长因子的表达,抑制肿瘤新生血管的生成,从而对人源化小鼠肝癌移植瘤起到抑制的作用。

    Abstract:

    Objective Explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumor. Methods 30 PD-1 humanized mice were selected and human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region of the mice 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); ② 17-DMAG group (intraperitoneal injection of 17-DMAG at 25 mg/kg, 3 times/week); ③ The cisplatin group (intraperitoneal injection of 20 mg/kg, 2 times per week), the experiment lasted for 4 week. After injection, the length and short diameter of the humanized mouse transplanted tumor were measured to calculate the volume, and the tumor mass were measured to calculate to calculate the tumor inhibition rate. At the same time, immunohistochemical methods 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 the cisplatin group were significantly reduced compared to 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 was no significant difference in tumor mass, volume, and tumor inhibition rate between the 17-DMAG group and the cisplatin group. The number of MVD labeled microvessels and VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group (P<0.05), and the 17-DMAG group was 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 vascular endothelial growth factor in liver cancer xenograft tissue, thereby inhibiting the generation of tumor neovascularization.

    参考文献
    [1] 李晓娟, 李兴杰, 孙慧伟, 等. 基于Image J软件对BALB/c突变卷毛鼠肝脏肿瘤的定量分析 [J]. 中国比较医学杂志, 2021, 31(11): 16-20.
    [2] Hollingshead M, Alley M, Burger AM, et al. In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative [J]. Cancer Chemothther Pharmacol, 2005, 56(2):115-125.
    [3] 彭树松, 阳静, 刘霆, 等. 17- DMAG 对肝癌HepG2细胞的作用研究 [J]. 中国现代医学杂志, 2012, 22(11): 30-35.
    [4] 李晓娟, 修叶, 李兴杰, 等. PD-1人源化小鼠构建繁殖与基因型鉴定 [J]. 实验动物科学, 2023, 40(4): 34-38.
    [5] Weidner N,Folkman J,Pozza F,et al. Tumor angio-genesis: a new significant and independent prognostic indicator in early-stage breast carcinoma [J]. J Nail Cancer lnst, 1992, 84: 1875-1887.
    [6] Dias FJ. Issa JP, Barbosa AP, et al. Effects of low-level laser irradiation in ultrastructural morphology,and immune expression of VEGF and VEGFR-2 of rat masseter muscle [J]. Micron, 2012, 43: 237-244.
    [7] Gooljarsingh LT, Fernandes C, Yan K, et al. A biochemical rationale for the anticancer effects of Hsp90 inhibitors: slow, tight binding inhibition by geldanamycin and its analogues [J]. Proc Natl Acad Sci USA, 2006, 103(20): 7625-7630.
    [8] Burrows F, Zhang H, Kamal A. Hsp90 activation and cell cycle regulation [J]. Cell Cycle, 2004, 3(12): 1530-1536.
    [9] 张钟元, 阎爱侠. Hsp90抑制剂的研究进展 [J]. 中国医药生物技术, 2021, 16(1): 41-50.
    [10] 高风彩, 郭荣, 田文亮, 等. HSP90 抑制剂17-DMAG对白血病细胞株K562增殖及凋亡的影响 [J]. 中国实验血液学杂志, 2017, 25(4): 998-1002.
    [11] 吴文辉, 朱佳成, 罗特东, 等. 热休克蛋白 90 抑制剂17-DMAG联合5-FU对人胃癌裸鼠移植瘤的抑制作用研究 [J]. 消化肿瘤杂志(电子版), 2015, 7(2): 99-105.
    [12] 肖隆斌, 吴文辉, 刘其龙. 17-二甲基胺乙基-17-去甲氧基格尔德霉素对人胃癌裸鼠移植瘤血管内皮生长因子表达的抑制作用 [J]. 中国病理生理杂志, 2010, 26(8): 1489-1493.
    [13] Chien CC, Kempson IM, Wang CL,et al. Complete microscale profiling of tumor microangiogenesis: a microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization [J]. Biotechnol Adv, 2013, 31: 396-401.
    [14] 廖坚松, 陈焕忠, 茹晃耀, 等. 17-DMAG 对人结直肠癌裸鼠移植瘤微血管形成的抑制作用 [J]. 新医学, 2014, 45(6): 364-367.
    [15] 汤颖, 叶增纯, 李灿明, 等. VEGF 对小鼠足细胞黏附性的影响及 PI3 K/Akt 信号通路在其中的作用 [J]. 新医学, 2013, 44: 671-675.
    [16] Kim IS, Kim JH. Heat Shock Protein as Molecular Targets for Breast Cancer Therapeutics [J]. J Breast Cancer, 2011, 14(3): 167-174.
    [17] Franco MC, Ye Y, Refakis CA,et al. Nitration of Hsp90 induces cell death [J]. Proc Natl Acad Sci USA, 2013, 110: 1102-1111.
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:228
  • 下载次数: 0
  • HTML阅读次数: 0
  • 引用次数: 0
历史
  • 收稿日期:2023-12-08
  • 最后修改日期:2024-03-20
  • 录用日期:2024-06-17
防诈骗提示!请勿点击不明链接或添加个人微信。编辑部所有邮箱后缀均为@cnilas.org
关闭