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原发性癌细胞培养模型对药物化学敏感性测定结果的影响:灌注微生物反应器系统作为细胞培养容器的应用。

The effect of primary cancer cell culture models on the results of drug chemosensitivity assays: the application of perfusion microbioreactor system as cell culture vessel.

作者信息

Hsieh Chia-Hsun, Chen Yi-Dao, Huang Shiang-Fu, Wang Hung-Ming, Wu Min-Hsien

机构信息

Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan ; Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan.

Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

Biomed Res Int. 2015;2015:470283. doi: 10.1155/2015/470283. Epub 2015 Jan 14.

Abstract

To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture condition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was adopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity assay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that minor environmental pH change could significantly affect the metabolic activity of cells, demonstrating the importance of stable culture condition for such assays. Moreover, the culture models could also significantly influence the metabolic activity and proliferation of cells. Furthermore, the choice of culture models might lead to different outcomes of chemosensitivity assays. Compared with the similar test based on tumor-level assays, the spheroid model could overestimate the drug resistance of cells to cisplatin, whereas the 2D and 3D culture models might overestimate the chemosensitivity of cells to such anticancer drug. In this study, the 3D culture models with same cell density as that in tumor samples showed comparable chemosensitivity assay results as the tumor-level assays. Overall, this study has provided some fundamental information for establishing a precise and faithful drug chemosensitivity assay.

摘要

为了精确且忠实地进行基于细胞的药物化学敏感性测定,需要一个定义明确且与生物学相关的培养条件。对于前者,采用了能够提供稳定培养条件的灌注微生物反应器系统。然而,对于后者,关于培养模型对原发性口腔癌细胞的生理学和化学敏感性测定结果的影响知之甚少。为了解决这些问题,进行了实验。结果表明,微小的环境pH变化会显著影响细胞的代谢活性,这表明稳定的培养条件对于此类测定的重要性。此外,培养模型也会显著影响细胞的代谢活性和增殖。此外,培养模型的选择可能导致化学敏感性测定的不同结果。与基于肿瘤水平测定的类似测试相比,球体模型可能会高估细胞对顺铂的耐药性,而二维和三维培养模型可能会高估细胞对此类抗癌药物的化学敏感性。在本研究中,具有与肿瘤样本相同细胞密度的三维培养模型显示出与肿瘤水平测定相当的化学敏感性测定结果。总体而言,本研究为建立精确且可靠的药物化学敏感性测定提供了一些基础信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd3/4310262/515ba6237389/BMRI2015-470283.001.jpg

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