• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

具有增强侵袭性的细胞球体，模拟人肝癌的体外和体内特性。

Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo.

机构信息

Gene Therapy Research Unit, Korea Research Institute of Bioscience and Biotechnology(KRIBB), 125 Gwahak-ro, Daejeon, Republic of Korea.

Genome Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB), 125 Gwahak-ro, Daejeon, Republic of Korea.

出版信息

Sci Rep. 2017 Sep 5;7(1):10499. doi: 10.1038/s41598-017-10828-7.

DOI:10.1038/s41598-017-10828-7
PMID:28874716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5585316/
Abstract

We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial-mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing.

摘要

我们设计了一种球体形成单元（SFU），用于高效且经济地生产细胞球体。我们使用 Huh7 肝癌细胞（HCC）优化了生成大型且均匀的肝癌细胞球体的方案。大型 Huh7 球体在中心和表面分别显示出凋亡和增殖信号。特别是，在细胞球体中检测到缺氧诱导因子-1α（HIF-1α）和 ERK 信号激活。为了减少核心坏死并增加致癌特征，我们将球体与 2%的人脐静脉内皮细胞（HUVEC）共培养。HUVEC 通过激活细胞因子信号转导，模拟肝癌中的基因表达，促进 HCC 相关基因和癌症干细胞标志物在 Huh7 球体中的增殖和基因表达。HUVEC 在体内激活上皮-间充质转化和血管生成途径，诱导 Huh7 球体中的血管生成和血管成熟。与单层细胞相比，含有 HUVEC 的大型 Huh7 细胞球体在更高浓度的抗癌药物（阿霉素和索拉非尼）中存活。我们的大型细胞球体提供了一种有用的 HCC 体外模型，可直观地观察抗癌药物测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/a378ee970555/41598_2017_10828_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/234b9a5af177/41598_2017_10828_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/4783e13133d9/41598_2017_10828_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/320b4ab33e8d/41598_2017_10828_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/36c267426f24/41598_2017_10828_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/64780a759d39/41598_2017_10828_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/a378ee970555/41598_2017_10828_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/234b9a5af177/41598_2017_10828_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/4783e13133d9/41598_2017_10828_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/320b4ab33e8d/41598_2017_10828_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/36c267426f24/41598_2017_10828_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/64780a759d39/41598_2017_10828_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c10/5585316/a378ee970555/41598_2017_10828_Fig6_HTML.jpg

相似文献

1
Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo.具有增强侵袭性的细胞球体，模拟人肝癌的体外和体内特性。
Sci Rep. 2017 Sep 5;7(1):10499. doi: 10.1038/s41598-017-10828-7.
2
Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma.三维混合细胞球体模拟肝癌中基质介导的化疗耐药性和侵袭性迁移。
Neoplasia. 2018 Aug;20(8):800-812. doi: 10.1016/j.neo.2018.05.008. Epub 2018 Jul 4.
3
Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma.患者来源的多细胞肿瘤球体，旨在优化肝细胞癌患者的治疗。
J Exp Clin Cancer Res. 2018 May 25;37(1):109. doi: 10.1186/s13046-018-0752-0.
4
Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma.长非编码 RNA UBE2CP3 通过激活 ERK1/2/HIF-1α/VEGFA 信号通路增强 HCC 细胞 VEGFA 的分泌，促进肝癌血管生成。
J Exp Clin Cancer Res. 2018 Jun 4;37(1):113. doi: 10.1186/s13046-018-0727-1.
5
HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment.在缺氧肿瘤微环境中，缺氧诱导因子-1α（HIF-1α）通过上调赖氨酰氧化酶样蛋白2（LOXL2）促进肝细胞癌中的血管生成拟态形成。
J Exp Clin Cancer Res. 2017 Apr 27;36(1):60. doi: 10.1186/s13046-017-0533-1.
6
Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma.人肝细胞癌的三维器官型培养模型
Sci Rep. 2016 Feb 16;6:21174. doi: 10.1038/srep21174.
7
Hepatocellular carcinoma cells and their fibrotic microenvironment modulate bone marrow-derived mesenchymal stromal cell migration in vitro and in vivo.肝细胞癌细胞及其纤维化微环境调节骨髓间充质基质细胞在体外和体内的迁移。
Mol Pharm. 2011 Oct 3;8(5):1538-48. doi: 10.1021/mp200137c. Epub 2011 Aug 19.
8
Activated hepatic stellate cells play pivotal roles in hepatocellular carcinoma cell chemoresistance and migration in multicellular tumor spheroids.活化的肝星状细胞在多细胞肿瘤球中发挥关键作用，促进肝癌细胞的化疗耐药性和迁移。
Sci Rep. 2016 Nov 17;6:36750. doi: 10.1038/srep36750.
9
EphA1 activation promotes the homing of endothelial progenitor cells to hepatocellular carcinoma for tumor neovascularization through the SDF-1/CXCR4 signaling pathway.EphA1激活通过SDF-1/CXCR4信号通路促进内皮祖细胞归巢至肝细胞癌，以实现肿瘤新生血管形成。
J Exp Clin Cancer Res. 2016 Apr 11;35:65. doi: 10.1186/s13046-016-0339-6.
10
Fatty acid binding protein 5 promotes tumor angiogenesis and activates the IL6/STAT3/VEGFA pathway in hepatocellular carcinoma.脂肪酸结合蛋白 5 促进肝癌血管生成，并激活 IL6/STAT3/VEGFA 通路。
Biomed Pharmacother. 2018 Oct;106:68-76. doi: 10.1016/j.biopha.2018.06.040. Epub 2018 Jun 26.

引用本文的文献

1
Unraveling the Effects of Epigallocatechin-3-gallate on Hepatocellular Carcinoma Cells: A Comparative Analysis of Monolayer vs Multicellular Tumor Spheroids.表没食子儿茶素-3-没食子酸酯对肝癌细胞的影响解析：单层细胞与多细胞肿瘤球体的比较分析
ACS Omega. 2025 Jul 31;10(31):34238-34253. doi: 10.1021/acsomega.5c00839. eCollection 2025 Aug 12.
2
Extracellular matrix regulation of cell spheroid invasion in a 3D bioprinted solid tumor-on-a-chip.三维生物打印固体肿瘤芯片中细胞球体浸润的细胞外基质调节。
Acta Biomater. 2024 Sep 15;186:156-166. doi: 10.1016/j.actbio.2024.07.040. Epub 2024 Aug 7.
3
Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-based model of the human liver for drug screening applications.

本文引用的文献

1
Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells.双酚A激活表皮生长因子受体（EGFR）和细胞外信号调节激酶（ERK），促进雌激素受体阴性炎症性乳腺癌细胞的增殖、肿瘤球形成及对EGFR通路抑制的抗性。
Carcinogenesis. 2017 Mar 1;38(3):252-260. doi: 10.1093/carcin/bgx003.
2
Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma.人肝细胞癌的三维器官型培养模型
Sci Rep. 2016 Feb 16;6:21174. doi: 10.1038/srep21174.
3
Co-culture of 3D tumor spheroids with fibroblasts as a model for epithelial-mesenchymal transition in vitro.
芯片上的肝球：用于药物筛选应用的基于球体的人肝模型的构建与表征
Biomicrofluidics. 2024 May 28;18(3):034105. doi: 10.1063/5.0210955. eCollection 2024 May.
4
Improvements in Maturity and Stability of 3D iPSC-Derived Hepatocyte-like Cell Cultures.三维诱导多能干细胞衍生的肝细胞样细胞培养物成熟度和稳定性的改善。
Cells. 2023 Sep 27;12(19):2368. doi: 10.3390/cells12192368.
5
Physical Properties and Cellular Metabolic Characteristics of 3D Spheroids Are Possible Definitive Indices for the Biological Nature of Cancer-Associated Fibroblasts.三维球体的物理特性和细胞代谢特征可能是癌症相关成纤维细胞生物学特性的明确指标。
Cells. 2023 Aug 28;12(17):2160. doi: 10.3390/cells12172160.
6
Physiologically relevant microsystems to study viral infection in the human liver.用于研究人类肝脏中病毒感染的生理相关微系统。
Front Microbiol. 2022 Sep 28;13:999366. doi: 10.3389/fmicb.2022.999366. eCollection 2022.
7
Role of Intracellular and Extracellular Annexin A1 in MIA PaCa-2 Spheroids Formation and Drug Sensitivity.细胞内和细胞外膜联蛋白A1在MIA PaCa-2球体形成和药物敏感性中的作用
Cancers (Basel). 2022 Sep 29;14(19):4764. doi: 10.3390/cancers14194764.
8
VEGF-mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma.血管内皮生长因子介导的肝癌二维和三维细胞培养模型中的肿瘤生长及上皮-间质转化
Oncol Lett. 2022 Jul 15;24(3):315. doi: 10.3892/ol.2022.13435. eCollection 2022 Sep.
9
Three-dimensional (3D) cell culture: a valuable step in advancing treatments for human hepatocellular carcinoma.三维（3D）细胞培养：推进人类肝细胞癌治疗的重要一步。
Cancer Cell Int. 2022 Jul 30;22(1):243. doi: 10.1186/s12935-022-02662-3.
10
Inhibition of eIF6 Activity Reduces Hepatocellular Carcinoma Growth: An In Vivo and In Vitro Study.抑制 eIF6 活性可降低肝癌生长：一项体内和体外研究。
Int J Mol Sci. 2022 Jul 13;23(14):7720. doi: 10.3390/ijms23147720.
将3D肿瘤球体与成纤维细胞共培养作为体外上皮-间质转化的模型。
Exp Cell Res. 2015 Jul 15;335(2):187-96. doi: 10.1016/j.yexcr.2015.05.016. Epub 2015 May 28.
4
Improved in vitro human tumor models for cancer gene therapy.
Hum Gene Ther. 2015 May;26(5):249-56. doi: 10.1089/hum.2015.028. Epub 2015 Apr 20.
5
Three-dimensional in vitro co-culture model of breast tumor using magnetic levitation.利用磁悬浮技术构建的乳腺肿瘤三维体外共培养模型
Sci Rep. 2014 Oct 1;4:6468. doi: 10.1038/srep06468.
6
Hydrogels to model 3D in vitro microenvironment of tumor vascularization.用于模拟肿瘤血管生成的3D体外微环境的水凝胶。
Adv Drug Deliv Rev. 2014 Dec 15;79-80:19-29. doi: 10.1016/j.addr.2014.06.002. Epub 2014 Jun 23.
7
Advanced cell culture techniques for cancer drug discovery.用于癌症药物发现的先进细胞培养技术。
Biology (Basel). 2014 May 30;3(2):345-67. doi: 10.3390/biology3020345.
8
Hypoxia and the extracellular matrix: drivers of tumour metastasis.缺氧与细胞外基质：肿瘤转移的驱动因素。
Nat Rev Cancer. 2014 Jun;14(6):430-9. doi: 10.1038/nrc3726. Epub 2014 May 15.
9
Vascular endothelial cells facilitated HCC invasion and metastasis through the Akt and NF-κB pathways induced by paracrine cytokines.血管内皮细胞通过旁分泌细胞因子诱导的 Akt 和 NF-κB 通路促进 HCC 的侵袭和转移。
J Exp Clin Cancer Res. 2013 Aug 13;32(1):51. doi: 10.1186/1756-9966-32-51.
10
Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing.开发一种用于体外药物测试的人类三维器官型皮肤-黑色素瘤球体模型。
Cell Death Dis. 2013 Jul 11;4(7):e719. doi: 10.1038/cddis.2013.249.