3D bioprinting-based single liver tumor spheroid analysis for aflatoxin B1-induced drug-resistant cancer cell

Abstract

Aflatoxin B1, found in a variety of foods, is a mycotoxin known to cause cancer. Therefore, humans may be exposed to it through their daily diet. In this study, a three-dimensional (3D) tumor spheroid model was developed via 3D bioprinting to examine whether exposure of HepG2 liver tumor spheroids to aflatoxin B1 can increase the population of drug-resistant liver cancer cells in a single tumor spheroid. Two biomarkers, CD133 (prominin-1) and aldehyde dehydrogenase 1 (ALDH1), were used to identify drug-resistant cancer cells formed in the single liver tumor spheroids. The induction of drug-resistant cancer cells in the single tumor spheroids was examined through single spheroid imaging and fluorescence-activated cell sorting (FACS). The increase of drug-resistant cancer cells, which was caused by aflatoxin B1 in a dose-dependent manner, was quantitatively monitored at the single tumor spheroid level using both methods. 3D bioprinting-fabricated single liver tumor spheroid model successfully determined drug-resistant liver cancer cells caused by aflatoxin B1