多层纸芯片乳腺癌组织微阵列用于抗肿瘤药物测试

引用本文: 刘未平, 林锦琼, 杜燕, 齐明月, 梁广铁, 杨娜, 刘大渔. 多层纸芯片乳腺癌组织微阵列用于抗肿瘤药物测试[J]. 分析化学, 2016, 44(4): 579-585. doi: 10.11895/j.issn.0253-3820.151025 shu

Citation: LIU Wei-Ping, LIN Jin-Qiong, DU Yan, QI Ming-Yue, LIANG Guang-Tie, YANG Na, LIU Da-Yu. Anti-Cancer Drug Testing Using Multi-Layer Paper-Supported Breast Cancer Tissue Array[J]. Chinese Journal of Analytical Chemistry, 2016, 44(4): 579-585. doi: 10.11895/j.issn.0253-3820.151025 shu

多层纸芯片乳腺癌组织微阵列用于抗肿瘤药物测试

刘未平 ^1, ,
林锦琼 ^1, ,
杜燕 ^1, ,
齐明月 ^1, ,
梁广铁 ^1,2, ,
杨娜 ^1,2, ,
刘大渔 ^{1,2,3,
,}

1.
¹ 广州医科大学附属广州市第一人民医院检验医学研究室, 广州 510180;
2.
² 广东省临床分子医学及分子诊断重点实验室, 广州 510180;
3.
³ 大连医科大学附属第二医院临床科研中心, 大连 116027

通讯作者: 刘大渔

基金项目:
本文系国家自然科学基金(Nos.81371649,81271730,81171418) (Nos.81371649,81271730,81171418)

广州市医药卫生科技项目(Nos.20121A021002,20121A011035)资助 (Nos.20121A021002,20121A011035)

摘要: 开发了一种多层纸芯片细胞培养平台,将乳腺癌细胞分别接种于多层的图形化纸芯片的亲水区,折叠后构建了仿真实体肿瘤。多层纸芯片覆以微孔薄膜,用以仿真血管内皮层。培养不同时间后,拆解多层纸芯片检测乳腺癌组织内各层面的细胞形态、存活率、细胞周期分布以及细胞内乳酸含量。实验结果显示,各层纸芯片培养的乳腺癌细胞存活率均高于80%,并形成了类组织结构。芯片乳腺癌组织内部呈酸化倾向,且酸化程度随着培养时间的延长而升高。与二维(2D)培养细胞相比较,纸芯片乳腺癌组织内细胞增殖比例显著降低(15% vs 60%)。多层纸芯片乳腺癌组织显示了更接近体内情况的药物反应机制,细胞存活率随阿霉素浓度升高呈现缓慢下降趋势,IC₅₀值显著高于2D培养细胞组(5.0μmol/L vs 1.144μmol/L)。这种多层纸芯片乳腺癌组织微阵列构建简便、仿真度高,有望成为抗肿瘤药物反应测试的有力工具。

关键词:

English

Anti-Cancer Drug Testing Using Multi-Layer Paper-Supported Breast Cancer Tissue Array

1.
¹ Department of Laboratory Medicine, Guangzhou First People's Hospital Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China;
2.
² Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China;
3.
³ Clinical Research Center, the Second Hospital Affiliated to Dalian Medical University, Dalian 116027, China

Corresponding author: 刘大渔

Received Date: 30 December 2015
Fund Project:
本文系国家自然科学基金(Nos.81371649,81271730,81171418)

广州市医药卫生科技项目(Nos.20121A021002,20121A011035)资助

Abstract: This paper describes a multi-layer paper-supported breast cancer tissue array. The paper-based microchip with arrayed hydrophilic spots was fabricated by wax printing. After cell seeding, the microchip was folded to form an artificial solid tumor, and the multilayer paper was covered by a layer of microporous membrane that mimics endothelial layer. After culturing the paper-supported breast cancer tissue for a certain period of time, the multi-layer device was unfold thus enabling detections of cell survival, proliferation, morphology and metabolism on different layers. Breast cancer cells cultured on paper had a survival rate >80% and aggregated into tumor spheroids. Intracellular lactic acid levels increased with the extension of culture time. Compared to two dimensional(2D) counterparts, the decreased fraction of S phase cell(15% vs 60%) was detected. The paper-supported breast cancer tissue showed a drug response mechanism similar to the tumor in vivo. Cancer cells within the tissue were less sensitive to doxorubicin and the IC₅₀ value detected was significantly higher than that obtained with 2D cultures(5μmol/L vs 1.14μmol/L). The multi-layer paper-supported breast cancer tissue array developed in this work featured simple tissue reconstruction and easy operation, thus providing an ideal tool for anti-cancer drug testing.

Key words:

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

多层纸芯片乳腺癌组织微阵列用于抗肿瘤药物测试

通讯作者: 刘大渔

English

Anti-Cancer Drug Testing Using Multi-Layer Paper-Supported Breast Cancer Tissue Array

Corresponding author: 刘大渔

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CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

多层纸芯片乳腺癌组织微阵列用于抗肿瘤药物测试

通讯作者: 刘大渔

English

Anti-Cancer Drug Testing Using Multi-Layer Paper-Supported Breast Cancer Tissue Array

Corresponding author: 刘大渔

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs