Development of a Breast-on-a-Chip Microfluidic Model to Assess the Effect of Palbociclib in MCF-7 and T47D Cancer Cells

TL;DR

A microfluidic breast-on-a-chip model was developed to study how Palbociclib affects breast cancer cells under controlled flow conditions.

Contribution

The study introduces a reproducible breast-on-a-chip system for evaluating drug responses and resistance markers under dynamic flow.

Findings

Palbociclib induced dose-dependent changes in cell viability, morphology, apoptosis, and PARP1 processing in MCF-7 and T47D cells.

The microfluidic system showed consistent biological responses across different setups under identical flow and temperature conditions.

Cytoskeletal disorganization and differential PARP1 processing were observed, aligning with known effects of CDK4/6 inhibition.

Abstract

What are the main findings?
A controlled perfusion (20 µL/h) was established, allowing simultaneous evaluation of proliferation, viability, cytoskeletal organization, apoptosis, and PARP1 differential processing in luminal breast cancer cells under flow conditions.Palbociclib treatment produced dose-dependent changes in cell viability, morphology, apoptotic response, and PARP1 processing in MCF-7 and T47D cells, with comparable biological response trends observed across distinct microfluidic setups operated under identical flow and temperature parameters.

A controlled perfusion (20 µL/h) was established, allowing simultaneous evaluation of proliferation, viability, cytoskeletal organization, apoptosis, and PARP1 differential processing in luminal breast cancer cells under flow conditions.

Palbociclib treatment produced dose-dependent changes in cell viability, morphology, apoptotic response, and PARP1 processing in MCF-7 and T47D cells, with comparable biological response trends observed across distinct microfluidic setups operated under identical flow and temperature parameters.

What are the implications of the main findings?
The well-controlled 2D microfluidic breast-on-a-chip system provides a robust and experimentally accessible framework for studying drug response and resistance-associated biomarkers under physiologically relevant dynamic conditions.This approach represents a scalable starting point for organ-on-a-chip applications and supports future integration of limited cell sources, including patient-derived samples, to improve translational relevance in anticancer drug screening.

The well-controlled 2D microfluidic breast-on-a-chip system provides a robust and experimentally accessible framework for studying drug response and resistance-associated biomarkers under physiologically relevant dynamic conditions.

This approach represents a scalable starting point for organ-on-a-chip applications and supports future integration of limited cell sources, including patient-derived samples, to improve translational relevance in anticancer drug screening.

Organ-on-a-chip devices combine microfabrication, tissue engineering, and microfluidics to recreate physiologically relevant microenvironments for in vitro studies. In this work, we validated a dynamic 2D breast-on-a-chip microfluidic bioassay operated at a controlled infusion rate of 20 µL/h to assess anticancer drug responses under defined flow conditions. Using Palbociclib as a reference compound, we evaluated proliferation, viability/apoptosis, cytoskeleton organization, and differential processing of the resistance-associated marker PARP1 in MCF-7 and T47D breast cancer cells. Under dynamic microfluidic conditions, Palbociclib induced dose-dependent effects, with the higher concentration (20 µM) consistently reducing cell proliferation and viability and increasing late apoptosis compared to 10 µM Palbociclib. Cytoskeletal disorganization was observed at both concentrations, while differential PARP1 processing patterns between MCF-7 and T47D cells were detected across doses. These responses are consistent with known effects of CDK4/6 inhibition and were reproducibly captured under controlled flow conditions. Overall, our results demonstrate that this breast-on-a-chip microfluidic model provides a reproducible and physiologically relevant in vitro platform for integrated assessment of drug efficacy and resistance-associated markers under dynamic perfusion.

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