Citation: SUN Wei, CHEN Yu-Qing, WANG Ming-Fang, WANG Yue-Rong, ZHANG Min, ZHANG Hong-Yang, HU Ping. Study on Drug Resistance to Tumor Cell in Oxygen Gradient and Co-culture Microfluidic Chip[J]. Chinese Journal of Analytical Chemistry, ;2020, 48(2): 180-186. doi: 10.19756/j.issn.0253-3820.191580 shu

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

1.
Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East-China University of Science and Technology, Shanghai 200237, China;
2.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

Received Date: 30 September 2019
Revised Date: 8 November 2019

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

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.
- Microfluidic chip,
- Tumor microenvironment,
- Oxygen gradient,
- Cell co-culture,
- Drug resistance
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沈阳化工大学材料科学与工程学院沈阳 110142