Int J Med Sci 2022; 19(8):1320-1333. doi:10.7150/ijms.74109 This issue

Research Paper

Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer

Kisho Ono1✉#, Kohei Sato1#, Tomoya Nakamura1, Yume Yoshida1, Shogo Murata1, Kunihiro Yoshida1, Hideka Kanemoto1, Koki Umemori1, Hotaka Kawai2, Kyoichi Obata1, Shoji Ryumon1, Kazuaki Hasegawa1, Yuki Kunisada1, Tatsuo Okui3, Soichiro Ibaragi1, Hitoshi Nagatsuka2, Akira Sasaki1

1. Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan.
2. Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan.
3. Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Ono K, Sato K, Nakamura T, Yoshida Y, Murata S, Yoshida K, Kanemoto H, Umemori K, Kawai H, Obata K, Ryumon S, Hasegawa K, Kunisada Y, Okui T, Ibaragi S, Nagatsuka H, Sasaki A. Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer. Int J Med Sci 2022; 19(8):1320-1333. doi:10.7150/ijms.74109. Available from https://www.medsci.org/v19p1320.htm

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Abstract

Graphic abstract

Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality.

Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared.

Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line.

Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods.

Keywords: oral cancer, spheroid, three-dimensional culture, anticancer drug