A 3D spheroid system to evaluate inhibitors of the ABCG2 transporter in drug uptake and penetration

Research Overview

The drug-efflux transporter ABCG2 helps multidrug-resistant tumors pump chemotherapy out of their cells, and no clinically effective ABCG2 inhibitor exists. This study introduced a 3D spheroid model for characterizing such inhibitors: spheroids overexpressing ABCG2 were self-assembled in nonadhesive micro-molds, incubated with the fluorescent transporter substrate Hoechst 33342, and followed by time-lapse fluorescence microscopy to quantify transporter-dependent efflux.

The system produced dose-response measurements for three inhibitors — Ko143, Iressa, and Elacridar — all acting within one hour. Elacridar showed a surprisingly long duration of effect, remaining active five hours after removal. Because the model works with multiple cell types and is image-based, it offers pharmacokinetic insight into transporter inhibitors and can be adapted to high-throughput screening.