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基于芯片肺的肺癌中表皮生长因子受体靶向抗肿瘤药物的探索性评估。

Exploratory Evaluation of EGFR-Targeted Anti-Tumor Drugs for Lung Cancer Based on Lung-on-a-Chip.

机构信息

Department of Thoracic Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen 518101, China.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510030, China.

出版信息

Biosensors (Basel). 2022 Aug 9;12(8):618. doi: 10.3390/bios12080618.

Abstract

In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.

摘要

在本研究中,我们使用三维(3D)打印技术制备了微流控芯片的模板,成功构建了聚二甲基硅氧烷(PDMS)肺芯片。芯片的上下通道由微孔膜隔开。上通道接种肺癌细胞,下通道接种血管内皮细胞,并持续用细胞培养基灌注。这种肺芯片可以模拟肺组织的微环境,实现两种细胞在不同水平的共培养。我们使用二维(2D)孔板和 3D 肺芯片来评估不同的 EGFR 靶向药物(吉非替尼、阿法替尼和奥希替尼)对肿瘤细胞的作用。3D 肺芯片在评估药物对 NCI-H650 的作用方面优于 2D 孔板,结果与现有临床数据更一致。对于原代肿瘤细胞,3D 肺芯片具有更多优势,因为它们模拟的条件更接近生理细胞微环境。肺芯片上对 EGFR 靶向药物的评估对个性化诊断和治疗以及药效评估具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/9405841/34595e806d41/biosensors-12-00618-g001.jpg

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