文章摘要
丛春晖,陈 斌,孙 丽,陈志红,赵媛媛,朱 伟.胃癌间质干细胞来源HGF对胃癌细胞生物学特性的影响[J].南京医科大学学报,2020,(2):185~190
胃癌间质干细胞来源HGF对胃癌细胞生物学特性的影响
Effects of HGF derived from gastric cancer mesenchymal stem cells on the biological characteristics of gastric cancer cells
投稿时间:2019-06-17  
DOI:10.7655/NYDXBNS20200207
中文关键词: 胃癌  间充质干细胞  肝细胞生长因子  程序性死亡受体⁃配体1
英文关键词: gastric cancer  mesenchymal stem cells  hepatocyte growth factor  PD⁃L1
基金项目:国家自然科学基金(81472334);江苏省社会发展重大研发项目(BE2017694)
作者单位
丛春晖 江苏大学医学院检验系 江苏 镇江 212013 
陈 斌 江苏大学医学院检验系 江苏 镇江 212013 
孙 丽 江苏大学医学院检验系 江苏 镇江 212013 
陈志红 江苏大学附属人民医院普外科 江苏 镇江 212001 
赵媛媛 江苏大学医学院检验系 江苏 镇江 212013 
朱 伟 江苏大学医学院检验系 江苏 镇江 212013 
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中文摘要:
      目的:观察胃癌间质干细胞(gastric cancer mesenchymal stem cell,GC?MSC)来源的肝细胞生长因子(hepatocyte growth factor,HGF)在胃癌细胞增殖、迁移及肿瘤形成中的作用。方法:采用CCK8实验检测胃癌细胞增殖活性;克隆形成实验检测胃癌细胞克隆形成能力;Transwell和细胞划痕实验检测胃癌细胞迁移能力;Western blot和流式细胞术检测胃癌细胞或癌组织的程序性死亡受体?配体1(programmed cell death?ligand 1,PD?L1)表达水平;构建BALB/c 裸鼠皮下成瘤模型,观察体内肿瘤形成情况;酶联免疫吸附试验(ELISA)检测血清及细胞培养上清中HGF水平;免疫组织化学染色(IHC)检测胃癌患者组织中HGF表达水平。结果:GC?MSC培养上清(culture medium of gastric cancer mesenchymal stem cell,GC?MSC?CM)中的HGF含量明显高于骨髓间质干细胞上清(culture medium of bone marrow mesenchymal stem cell,BM?MSC?CM)(P < 0.05)。GC?MSC?CM能够促进胃癌细胞增殖、迁移及克隆形成,并且这种促进作用能被HGF中和抗体明显抑制。GC?MSC?CM还明显促进胃癌细胞PD?L1表达,且能被HGF中和抗体抑制。此外,外源性的HGF也可以促进胃癌细胞增殖及PD?L1表达。临床胃癌患者治疗前血清HGF含量明显高于健康人血清HGF水平(P < 0.05)。结论:GC?MSC?CM来源的HGF在促胃癌细胞增殖、迁移、克隆形成以及PD?L1表达和肿瘤形成中发挥重要作用,其有可能成为胃癌防治的潜在分子靶标。
英文摘要:
      Objective:This stady aims to observe the role of hepatocyte growth factor(HGF) derived from gastric cancer mesenchymal stem cells(GC?MSC)in the proliferation,migration and tumor formation of gastric cancer cells. Methods:The proliferation activity of gastric cancer cells was detected with CCK8 assay. The colony forming ability of gastric cancer cells was analyzed via colony formation assay. Transwell assay and cell wound scratch assay were used to measure the migration ability of gastric cancers. By methods of Western blot and flow cytometry,we detected the expression of programmed cell death?ligand 1(PD?L1)in gastric cancer cells or cancer tissues. BALB/c nu/nu subcutaneous tumor model was constructed to observe tumor formation in vivo. The expression levels of HGF in serum and culture media were determined by ELISA,and protein levels of HGF in tissues of gastric cancer patients and healthy people were detected by immunohistochemistry. Results:The content of HGF in culture medium of gastric cancer mesenchymal stem cells(GC?MSC?CM) was significantly higher than that in culture medium of bone marrow mesenchymal stem cell(BM?MSC?CM)(P < 0.05). GC?MSC?CM treatment enhanced the proliferation,migration and colony formation of gastric cancer cells,and the promoting effect could be inhibited by HGF blockade. GC?MSC?CM could also promote the expression of PD?L1 in gastric cancer cell lines,and the proportion of PD?L1 positive cells decreased after HGF inhibition. In addition,exogenous HGF could also promote proliferation and PD?L1 expression of gastric cancer cells. The serum HGF levels in gastric cancer patients before therapy were significantly higher than those in healthy people(P < 0.05). Conclusion:GC?MSC?CM?derived HGF plays an important role in promoting gastric cancer cells proliferation,migration,colony formation,PD?L1 expression and tumor formation,which may become apotential molecular target for gastric cancer prevention and treatment.
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