Abstract |
Drug resistance in chemotherapy has been greatly challenging for cancer treatment. Research has revealed that extracellular vesicles (EVs) secreted by drug-resistant cells could induce chemoresistance in susceptible cells. However, there are few ways to give direct evidence of it. Herein, we have proposed a microchip-based system to study the drug resistance of a wild-type human lung adenocarcinoma cell line (A549/WT) induced by EVs derived from A549/DDP cells that are resistant to cisplatin (DDP) inherently. EVs derived from A549/DDP were proved to be the crucial factor that enhanced the resistance of A549/WT to DDP through live and dead cell staining, cell viability testing, and immunofluorescence of P-glycoprotein in the off-chip assay. Then, it was further validated that drug resistance of A549/WT cells to DDP significantly increased after being cocultured with A549/DDP cells within 96 h in the on-chip assay. These findings proved that the change of A549/WT drug resistance was caused by intercellular interaction, which was mainly mediated by EVs. In addition, we successfully reversed the EV-induced drug resistance of A549/WT cells by combining DDP and metformin, a hypoglycemic drug with low cytotoxicity when used alone. This microchip system provides a novel tool that has great potential for the investigation of cell interaction, drug resistance, and the tumor microenvironment in fundamental and clinical medicine.
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Authors | Tianyuan Fang, Wei Lu, Jingfeng Zhang, Ke Ge, Zhanhong Chen, Min Wang, Bo Yao |
Journal | Analytical chemistry
(Anal Chem)
Vol. 94
Issue 48
Pg. 16919-16926
(12 06 2022)
ISSN: 1520-6882 [Electronic] United States |
PMID | 36420757
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cisplatin
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Topics |
- Humans
- Drug Resistance, Neoplasm
- Lung Neoplasms
(pathology)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Cell Line, Tumor
- Apoptosis
- Cisplatin
(pharmacology, therapeutic use)
- Extracellular Vesicles
(metabolism)
- Tumor Microenvironment
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