3D Bioprinted Multidrug Resistance (MDR)-Dependent Tumor Spheroids

Area of Science:

• Biotechnology
• Cancer Research
• Pharmacology

Background:

• Multidrug resistance (MDR) in cancer cells is a major challenge in chemotherapy, driven by ATP-binding cassette (ABC) transporters.
• Accurate drug screening requires consideration of varying MDR levels in different cancer types.
• Tailoring chemotherapy dosage based on individual MDR profiles is crucial for treatment efficacy.

Purpose of the Study:

• To establish a 3D bioprinting-based platform for evaluating anticancer drug efficacy.
• To investigate the correlation between MDR phenotypes and drug response in tumor spheroids.
• To demonstrate the utility of this platform in drug discovery and personalized medicine.

Main Methods:

• Fabrication of three-dimensional (3D) tumor spheroids from HeLa, HepG2, and A549 cells using 3D bioprinting.
• Characterization of MDR phenotypes (MRP1 and BCRP expression) in the fabricated spheroids.
• Quantitative assessment of doxorubicin (DOX) efficacy using EC50 values against 2D cells and 3D spheroids, with and without ABC transporter inhibitors.

Main Results:

• 3D bioprinted tumor spheroids successfully retained their native MDR phenotypes.
• Doxorubicin (DOX) showed significantly higher EC50 values (over 2-fold) in 3D spheroids compared to 2D cells.
• DOX efficacy in spheroids was proportional to ABC transporter expression levels, with A549 spheroids exhibiting the highest resistance.
• ABC transporter inhibitors (MK-571 and NOV) significantly reduced DOX EC50 values in resistant spheroids.

Conclusions:

• The 3D bioprinting platform effectively models cancer MDR phenotypes.
• This platform enables quantitative evaluation of anticancer drug efficacy, accounting for MDR.
• The findings support the development of personalized chemotherapy strategies and improved drug screening processes.