Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.

Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.
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DOI:
10.1007/s10529-016-2035-1
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发表时间:
2016-08
影响因子:
2.7
通讯作者:
Cui Z
Cui Z
中科院分区:
工程技术4区
文献类型:
--
作者:
Wan X;Li Z;Ye H;Cui Z

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建立基于TIssueFlex系统的体外灌流三维(3D)球体模型,用于抗癌药物疗效测试,以模拟具有固有O2、营养和代谢物梯度的血管微组织,并提供比传统静态培养孔板中传统的体外肿瘤模型更准确的药物毒性和疗效预测。灌流的癌细胞球体模型在较长的培养时间(17天)内显示出较高的细胞存活率和球体直径的增加。对三种具有不同细胞毒作用机制的抗癌药物进行了检测。在灌流中,传统的细胞毒性药物5-氟尿嘧啶的细胞毒性较低,而微管干扰物紫杉醇对球体完整性的干扰较大。对于低氧依赖药物替拉帕明,静态培养和灌流培养之间没有显著差异。该灌流培养为癌细胞的生长提供了更好的动态平衡,为长期药物试验提供了一个更可控的工作平台。本文的在线版本(doi:10.1007/s10529-0162035-1)包含补充材料,授权用户可以使用。
To build an in vitro-perfused, three-dimensional (3D) spheroid model based on the TissueFlex system for anti-cancer drug efficacy testing in order to mimic avascular micro-tissues with inherent O2, nutrient and metabolite gradients, and to provide a more accurate prediction of drug toxicity and efficacy than traditional in vitro tumour models in conventional static culture well plates. The perfused cancer spheroid model showed higher cell viability and increased diameter of spheroids over a relatively long culture period (17 days). Three anti-cancer drugs with different cytotoxic mechanisms were tested. In perfusion, lower cytotoxicity was observed for traditional cytotoxic drug 5-fluorouracil and microtubule-interfering, paclitaxel, showed greater interruption of spheroid integrity. For the hypoxic-dependent drug, tirapazamine, there was no significant difference observed between static and perfusion cultures. The perfusion culture provides a better homeostasis for cancer cell growth in a more controllable working platform for long-term drug testing. The online version of this article (doi:10.1007/s10529-016-2035-1) contains supplementary material, which is available to authorized users.