3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained.
3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained.
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DOI：
10.1038/srep19103
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发表时间：
2016-01-11
影响因子：
4.6
通讯作者：
Tesei A
中科院分区：
文献类型：
--
作者：
Zanoni M;Piccinini F;Arienti C;Zamagni A;Santi S;Polico R;Bevilacqua A;Tesei A
由处于不同增殖和代谢状态的细胞组成的椭圆形肿瘤模型对于开发新的抗癌策略的潜力已经得到充分证明。然而，文献中很少或根本没有关于使用3D模型的实验产生的数据的重现性问题的信息。我们的分析使用了一种新的开源软件，能够对3D肿瘤集落进行自动图像分析，结果表明，许多形态参数影响大球体对治疗的反应。特别是，我们发现椭球体的体积和形状都可能是可变性的一个来源。我们还比较了一些专门为3D模型设计的商业上可用的生存能力分析。总之，我们的数据表明，在用于细胞毒性试验之前，需要预先选择体积和形状均一的肿瘤球体，以将数据的可变性降低到最小。此外，我们确定并验证了一项细胞毒性试验，该试验能够为不同类型的治疗对直径达650 μm的大肿瘤球体的损伤提供有意义的数据。
The potential of a spheroid tumor model composed of cells in different proliferative and metabolic states for the development of new anticancer strategies has been amply demonstrated. However, there is little or no information in the literature on the problems of reproducibility of data originating from experiments using 3D models. Our analyses, carried out using a novel open source software capable of performing an automatic image analysis of 3D tumor colonies, showed that a number of morphology parameters affect the response of large spheroids to treatment. In particular, we found that both spheroid volume and shape may be a source of variability. We also compared some commercially available viability assays specifically designed for 3D models. In conclusion, our data indicate the need for a pre-selection of tumor spheroids of homogeneous volume and shape to reduce data variability to a minimum before use in a cytotoxicity test. In addition, we identified and validated a cytotoxicity test capable of providing meaningful data on the damage induced in large tumor spheroids of up to diameter in 650 μm by different kinds of treatments.