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三维球体作为癌症研究的体外临床前模型

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research.

作者信息

Pinto Bárbara, Henriques Ana C, Silva Patrícia M A, Bousbaa Hassan

机构信息

Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), Instituto Universitário de Ciências da Saúde (IUCS), 4585-116 Gandra PRD, Portugal.

Instituto Nacional de Engenharia Biomédica (INEB), Universidade do Porto, 4099-002 Porto, Portugal.

出版信息

Pharmaceutics. 2020 Dec 6;12(12):1186. doi: 10.3390/pharmaceutics12121186.

DOI:10.3390/pharmaceutics12121186
PMID:33291351
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7762220/
Abstract

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell-cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

摘要

大多数癌症生物学家在进行体内测试之前,仍依赖传统的二维(2D)单层培养技术来体外测试抗肿瘤药物。然而,绝大多数有前景的临床前药物在实际肿瘤患者中疗效甚微或没有疗效,从而延误了成功治疗方法的发现。这是因为二维培养缺乏细胞间接触和天然肿瘤微环境,而这对肿瘤信号传导和药物反应至关重要,从而导致与真实肿瘤相比恶性表型减弱。从这个意义上说,能更好地模拟体内细胞环境的癌细胞三维(3D)培养,作为科学准确且低成本的癌症模型,在转向昂贵且耗时的动物模型之前,用于临床前筛选和测试新的候选药物。在此,我们全面概述三维肿瘤系统,并重点介绍球体构建策略和靶向治疗评估工具,着重阐述它们在癌症研究中的适用性。还讨论了三维培养在评估纳米药物治疗效果方面适用性的实例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/7762220/ff22a809f1a5/pharmaceutics-12-01186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/7762220/48955675d51d/pharmaceutics-12-01186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/7762220/ff22a809f1a5/pharmaceutics-12-01186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/7762220/48955675d51d/pharmaceutics-12-01186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/7762220/ff22a809f1a5/pharmaceutics-12-01186-g002.jpg

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