Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues
Related Experiment Video
Updated: Jun 29, 2025
Microfluidic Device for Recreating a Tumor Microenvironment in Vitro
Published on: November 20, 2011
Wanyoung Lim1, Inwoo Hwang2, Jiande Zhang3
1Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
Abstract:
Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.
Insights
Chemoresistance in triple-negative breast cancer (TNBC) arises from failed epigenetic control of the NUPR1/HDAC11 axis. This study rapidly induced doxorubicin-resistant (DOXR) cells, revealing NUPR1 as a marker for poor clinical outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Chemoresistance is a primary driver of cancer treatment failure.
- The cellular response to therapeutic stress and the development of resistance remain incompletely understood.
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and limited treatment options.
Purpose of the Study:
- To investigate the mechanisms underlying the rapid development of chemoresistance in TNBC cells.
- To explore the role of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis in chemoresistance.
- To establish a microfluidic model for inducing and studying chemoresistance.
Main Methods:
- Utilized a microfluidic device to generate gradients of doxorubicin (DOX) and medium, inducing doxorubicin-resistant (DOXR) cells from TNBC cells within 11 days.
- Established in vivo chemoresistant xenograft models.
- Performed unbiased genome-wide transcriptome analysis.
- Analyzed patient data and tissue samples.
Main Results:
- Successfully induced DOXR cells from TNBC cells using the microfluidic chip in 11 days.
- Identified failed epigenetic control of the NUPR1/HDAC11 axis as the mechanism of chemoresistance.
- Demonstrated that high NUPR1 expression correlates with poor clinical outcomes in cancer patients.
- Observed that the microfluidic chip can rapidly increase tumor heterogeneity and chemoresistance.
Conclusions:
- The microfluidic chip provides a rapid method for inducing chemoresistant cells, enhancing tumor heterogeneity.
- The NUPR1/HDAC11 axis is a critical regulator of chemoresistance in TNBC.
- Targeting the epigenetic control of the NUPR1/HDAC11 axis may offer novel therapeutic strategies for TNBC.
