文献类型：期刊文献

中文题名：基于氧气梯度共培养芯片的肿瘤细胞抗药性研究

英文题名：Study on Drug Resistance to Tumor Cell in Oxygen Gradient and Co-culture Microfluidic Chip

作者：孙威[1];陈雨晴[1];汪明芳[1];王月荣[1];张敏[2];章弘扬[1];胡坪[1]

机构：[1]上海市功能性材料化学重点实验室,华东理工大学化学与分子工程学院,上海200237;[2]华东理工大学药学院上海市新药设计重点实验室,上海200237

年份：2020

卷号：48

期号：2

起止页码：180

中文期刊名：分析化学

外文期刊名：Chinese Journal of Analytical Chemistry

收录：CSTPCD;;EI(收录号：20200608128355);Scopus;WOS:【SCI-EXPANDED(收录号:WOS:000515080700006)】；北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：This work was supported by the National Natural Science Foundation of China (No. 81973285).

语种：中文

中文关键词：微流控芯片;肿瘤微环境;氧气梯度;细胞共培养;抗药性

外文关键词：Microfluidic chip;Tumor microenvironment;Oxygen gradient;Cell co-culture;Drug resistance

摘要：肿瘤微环境是一个复杂的体系,对肿瘤的发展、侵袭和转移起至关重要的作用。本研究利用一个简单的氧气梯度芯片构建了体外肿瘤缺氧微环境模型。此芯片由产生氧气梯度的蛇形通道和用于小鼠肝癌细胞(Hepa1-6细胞)与肝星状细胞(JS-1细胞)共培养的3个平行通道组成,通过在肿瘤细胞生长的区域制造氧气梯度模拟肿瘤缺氧微环境。利用此芯片,开展了Hepa1-6细胞对紫杉醇和替拉扎明(TPZ)的抗药性研究,并从分子机制上分析导致抗药性的可能原因。结果表明,芯片所产生的氧气梯度的浓度范围为2.3%~16.7%。在缺氧条件下,共培养的Hepa1-6细胞在TPZ作用下存活率显著下降,但对紫杉醇产生抗药性。免疫荧光分析结果表明,缺氧及共培养可提高细胞因子TIMP-1与TGF-β的表达,促使JS-1细胞活化,进而增强Hepa1-6细胞对紫杉醇的抗药性。
Tumor microenvironment is a complex system,and it is of great importance in development,invasion and metastasis of tumor.In this work,an in vitro tumor hypoxic microenvironment model was constructed using an oxygen gradient microfluidic chip.The microfluidic chip was composed of two parts:one was a serpentine shape channel to generate oxygen gradient by a chemical reaction,the other was a three-parallel channel for the co-culture of cancer cells(Heap1-6 cells)and hepatic stellate cells(JS-1 cells).The oxygen gradient was made in cancer cells to simulate hypoxic tumor microenvironment,and then a drug-resistance study on paclitaxel and tirapazamine(TPZ)in hepa1-6 cells was performed and the potential reason of the drug resistance was analyzed by molecular mechanism.The result showed that the oxygen gradient was 2.3%-16.7%on chip.The Hepa1-6 cells expressed paclitaxel resistance in hypoxic condition,but cell viability was significant down due to the effect of TPZ.The results of immunofluorescence assay showed hypoxia and co-culture could promote the expression of TIMP-1 and TGF-β,induce the activation of JS-1 cell and then enhance the drug resistance of Hepa1-6 cell to paclitaxel.