Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Apr 15, 2026; 18(4): 116097
Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.116097
Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.116097
Morphological and functional responses of three-dimensional-cultured colorectal cancer spheres to anticancer drugs
Yusuke Yoshimura, Seiichi Shinji, Yutaro Ogawa, Takeshi Yamada, Akihisa Matsuda, Kay Uehara, Yasuyuki Yokoyama, Goro Takahashi, Takuma Iwai, Toshimitsu Miyasaka, Shintaro Kanaka, Takanori Matsui, Koki Hayashi, Hiroshi Yoshida, Department of Gastroenterological Surgery, Nippon Medical School, Bunkyo-ku 113-8603, Tokyo, Japan
Yusuke Yoshimura, Seiichi Shinji, Yutaro Ogawa, Masakazu Fujiwara, Yuuki Shichi, Toshiyuki Ishiwata, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi-ku 173-0015, Tokyo, Japan
Tomio Arai, Department of Pathology, Tokyo Metropolitan Institute for Geriatrics and Geronto
Author contributions: Yoshimura Y, Iwai T, and Shinji S conceptualized the study; Yoshimura Y, Ogawa Y, Shichi Y, and Fujiwara M were responsible for the investigation and the study’s methodology; Yamada T, Matsuda A, Uehara K, Ogawa Y, Takahashi G, Iwai T, Miyasaka T, Kanaka S, Matsui T, Hayashi K, Yoshimura Y, Arai T, and Yoshida H were responsible for the study’s resources; Yoshimura Y, Iwai T, and Shinji S were responsible for the writing - original draft; all authors were responsible for writing - review and editing; Iwai T and Shinji S supervised the study; Yamada T, Matsuda A, Uehara K, Ogawa Y, Takahashi G, Iwai T, Miyasaka T, Kanaka S, Hayashi K, Yokoyama Y, Arai T, and Yoshida H were responsible for the study validation.
Supported by the JSPS KAKENHI (Grants-in-Aid for Scientific Research C), No. 21K08744, No. 24K11881, No. 25K12018, No. 22K08882, and No. 22K08835.
Institutional review board statement: This study did not include any human or animal participants. Only established human cell lines obtained from a cell bank were used; therefore, institutional review board approval was not required.
Conflict-of-interest statement: The authors declare no conflicts of interest, including financial, personal, political, intellectual, or religious interests related to this work.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Seiichi Shinji, MD, PhD, Associate Professor, Department of Gastroenterological Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku 113-8603, Tokyo, Japan. s-shinji@nms.ac.jp
Received: November 3, 2025
Revised: November 28, 2025
Accepted: January 14, 2026
Published online: April 15, 2026
Processing time: 157 Days and 8.5 Hours
Revised: November 28, 2025
Accepted: January 14, 2026
Published online: April 15, 2026
Processing time: 157 Days and 8.5 Hours
Core Tip
Core Tip: This study analyzed the effects of 5-fluorouracil, irinotecan, and oxaliplatin on three-dimensionally cultured colorectal adenocarcinoma (CRAC) spheres. Using cell viability assays, apoptosis detection, and quantitative reverse transcriptase PCR, we found that the residual spheres displayed increased expression of cancer stem cell and epithelial-mesenchymal transition markers, with distinct profiles between epithelial (HCT-15) and mesenchymal (SW480) types. These results indicate that CRAC spheres that survive anticancer drug treatment acquire hybrid epithelial-mesenchymal phenotypes and stem cell-like features, providing insights into the mechanisms of drug tolerance and cancer recurrence in colorectal cancer.