Page 369 - IJB-9-6

International

Journal of Bioprinting

RESEARCH ARTICLE
3D bioprinting-based single liver tumor spheroid

analysis for aflatoxin B1-induced drug-resistant
cancer cell

Viet Phuong Cao, Sera Hong, and Joon Myong Song *

College of Pharmacy, Seoul National University, Seoul 08826, South Korea

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.
*Corresponding author:
Joon Myong Song Keywords: 3D bioprinting; Single tumor spheroid imaging; Aflatoxin B1;
(jmsong@snu.ac.kr)
Drug-resistant cancer cell
Citation: Cao VP, Hong S,
Song JM, 2023, 3D bioprinting-
based single liver tumor spheroid
analysis for aflatoxin B1-induced 1. Introduction
drug -resistant cancer cell. Int J
Bioprint, 9(6): 0985. Cancer stem cells (CSCs) are known to be responsible for tumors’ resistance to
https://doi.org/10.36922/ijb.0985 chemotherapies and radiotherapies, which lead to cancer treatment failure and cancer
Received: May 24, 2023 recurrence. CSCs have recently emerged as one of the most common targets for novel
Accepted: July 1, 2023 innovations in cancer therapies [1-4] . The distinctive characteristics and unique phenotype
Published Online: August 18, 2023
of CSCs are acquired as a result of abnormality in many pathways [5,6] , including
Copyright: © 2023 Author(s). STAT3, Wnt/TCF, or NF-κB. Besides, transcription factors such as KLF4, c-MYC, and
This is an Open Access article NANOG are overexpressed in CSCs, leading to the ability of metastasis, tumorigenesis,
distributed under the terms of the
Creative Commons Attribution cell proliferation, and self-renewal, respectively. Among these characteristics,
License, permitting distribution, drug resistance is one of the key features, the mechanism of which involves many
and reproduction in any medium, approaches [7,8] . Common processes include enhanced ATP-binding cassette transporter
provided the original work is
properly cited. (ABC transporter) activity, by which the cells are protected by chemotherapy agents like
doxorubicin or methotrexate, and apoptosis prevention via Rho-ROCK pathway.
Publisher’s Note: AccScience
Publishing remains neutral with The stem-like characteristics of CSCs are preserved and displayed by an array of
regard to jurisdictional claims in
published maps and institutional markers, which are abnormally expressed because of modification in gene regulations.
affiliations. For example, CD44, a common marker in many cancer types, has been proven to not

Volume 9 Issue 6 (2023) 361 https://doi.org/10.36922/ijb.0985