Paper 2024, analytical chemistry, U‑Shape Pillar Strip for 3D Cell-Lumped Or…
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ABSTRACT:
Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients.
Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in
physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a
U-shape pillar strip for a 3D cell-lumped organoid model (3DCOM) to study the effects of hypoxia on lung cancer in a highthroughput manner. We developed a U-pillar strip that facilitates
the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The
results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the Ushape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.
Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients.
Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in
physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a
U-shape pillar strip for a 3D cell-lumped organoid model (3DCOM) to study the effects of hypoxia on lung cancer in a highthroughput manner. We developed a U-pillar strip that facilitates
the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The
results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the Ushape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.
2024, NPJ Precision Oncology, Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion