纳米氧化锌抑制骨肉瘤细胞增殖、血管形成和肺转移的相关机制研究  

Study on the mechanism of zinc oxide nanoparticles inhibiting the cell proliferation,angiogenesis and lung metastasis of osteosarcoma

作　　者：何观平 HE Guanping(Department of Orthopedics,Beijing Chao-Yang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院骨科,北京100020

出　　处：《现代肿瘤医学》2025年第1期7-13,共7页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82203893)。

摘　　要：目的:探讨体内外纳米氧化锌对骨肉瘤细胞增殖、血管形成以及肺转移的影响。方法:取对数生长期SaoS-2和143B骨肉瘤细胞系,分为实验组和对照组。实验组分别加入不同浓度(10μmol/L、20μmol/L)纳米氧化锌处理,对照组不干预。培养24 h后,采用CCK-8和克隆形成实验检测细胞增殖活性;血管形成实验检测血管生成能力;Western blot检测VEGF-a蛋白表达水平;裸鼠胫骨原位骨肉瘤模型评价体内原位骨肉瘤生长、肺转移以及生存期变化;HE染色和免疫组化方法检测肿瘤组织VEGF-a以及Ki-67蛋白表达水平。结果:CCK-8细胞增殖实验显示,纳米氧化锌处理组SaoS-2以及143B骨肉瘤细胞从第三天开始增殖抑制率明显低于对照组,并且显示出时间和浓度依赖性。细胞克隆实验同样显示,在第10天时,纳米氧化锌处理SaoS-2以及143B骨肉瘤细胞细胞群落数目明显少于对照组。血管形成实验结果显示,与对照组相比,纳米氧化锌处理能够明显抑制脐静脉内皮细胞血管生成能力。Western blot结果显示,纳米氧化锌处理骨肉瘤细胞内VEGF-a蛋白表达显著下调。裸鼠体内胫骨原位骨肉瘤模型结果显示,纳米氧化锌处理组显著抑制裸鼠胫骨原位和肺转移骨肉瘤生长、肿瘤组织内VEGF-a和Ki-67蛋白表达以及延长裸鼠生存期。结论:纳米氧化锌能够抑制骨肉瘤细胞增殖、血管形成以及提高预后,其机制可能与下调VEGF-a蛋白表达相关。Objective:To investigate the effect of zinc oxide nanoparticles on proliferation,angiogenesis and lung metastasis of osteosarcoma in vitro and in vivo.Methods:The SaoS-2 and 143B osteosarcoma cell lines were divided into the experimental group and control group.The experimental group was treated with zinc oxide nanoparticles of different concentrations(10μmol/L,20μmol/L).After 24 hours,the cell proliferation activity was detected by CCK-8 and clone formation assay,the ability of angiogenesis was detected by tube forming experiment,the expression of VEGF-a protein was detected by Western blot.The growth,lung metastasis and survival of tibial osteosarcoma in vivo were evaluated in nude mouse model,HE staining and immunohistochemistry were used to detect the expression of VEGF-a and Ki-67 protein in tumor tissues.Results:CCK-8 experiment showed that the proliferation inhibition rate of SaoS-2 and 143B osteosarcoma cells in the zinc oxide nanoparticles treatment group was significantly lower than that in the control group from the third day,and showed a time and concentration dependent manner.Clone formation experiment also showed that on the 10th day,the number of cell communities of SaoS-2 and 143B osteosarcoma cells treated with zinc oxide nanoparticles was significantly less than that of the control group.The results of tube forming experiment showed that compared with the control group,zinc oxide nanoparticles could significantly inhibit the angiogenesis of human umbilical vein endothelial cells.Western blot results showed that the expression of VEGF-a protein in osteosarcoma cells treated with zinc oxide nanoparticles was significantly downregulated.The results of in vivo model of tibial osteosarcoma in nude mice showed that the zinc oxide nanoparticles treatment group significantly inhibited the growth of tibial osteosarcoma in situ and lung metastasis,the expression of VEGF-a and Ki-67 proteins in tumor tissue but prolonged the survival time of nude mice.Conclusion:Zinc oxide nanoparticles can inhibit the p

关 键 词：纳米氧化锌 骨肉瘤 增殖 血管形成 肺转移 

分 类 号：R738.1[医药卫生—肿瘤]