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

Kisho Ono, Kohei Sato, Tomoya Nakamura, Yume Yoshida, Shogo Murata, Kunihiro Yoshida, Hideka Kanemoto, Koki Umemori, Hotaka Kawai, Kyoichi Obata, Shoji Ryumon, Kazuaki Hasegawa, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1320-1333
Number of pages14
JournalInternational journal of medical sciences
Issue number8
Publication statusPublished - 2022


  • anticancer drug
  • oral cancer
  • spheroid
  • three-dimensional culture

ASJC Scopus subject areas

  • Medicine(all)


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