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Suzuki S, Iwaizumi M, Yamada H, et al. . Oncotarget. 2017;9(14):11477-11488doi: 10.18632/oncotarget.22484.
Suzuki, S., Iwaizumi, M., Yamada, H., Sugiyama, T., Hamaya, Y., Furuta, T., Kanaoka, S., Sugimura, H., Miyajima, H., Osawa, S., Carethers, J. M., & Sugimoto, K. (2018). . Oncotarget, 9(14), 11477-11488. https://doi.org/10.18632/oncotarget.22484
Suzuki, Satoshi, et al. "." Oncotarget vol. 9,14 (2018): 11477-11488. doi: https://doi.org/10.18632/oncotarget.22484
Suzuki S, Iwaizumi M, Yamada H, Sugiyama T, Hamaya Y, Furuta T, Kanaoka S, Sugimura H, Miyajima H, Osawa S, Carethers JM, Sugimoto K. . Oncotarget. 2017 Nov 15;9(14):11477-11488. doi: 10.18632/oncotarget.22484. eCollection 2018 Feb 20. PMID: 29545913; PMCID: PMC5837757.
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Oncotarget. 2017 Nov 15;9(14):11477-11488. doi: 10.18632/oncotarget.22484. eCollection 2018 Feb 20.

[No title available]

Oncotarget

Satoshi Suzuki, Moriya Iwaizumi, Hidetaka Yamada, Tomohiro Sugiyama, Yasushi Hamaya, Takahisa Furuta, Shigeru Kanaoka, Haruhiko Sugimura, Hiroaki Miyajima, Satoshi Osawa, John M Carethers, Ken Sugimoto

Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  2. Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  3. Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  4. Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu, Japan.
  5. International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  6. Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  7. Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 29545913 PMCID: PMC5837757 DOI: 10.18632/oncotarget.22484

Abstract

BACKGROUNDS: Trifluridine is an active antitumor component of TAS-102 that resembles 5-fluorouracil. Although patients with advanced colorectal cancer (CRC) exhibiting a mismatch repair (MMR) deficiency reportedly do not benefit from 5-fluorouracil-based chemotherapy and we previously reported that truncated methyl-CpG binding domain protein 4 (MBD4) enhances 5-fluorouracil cytotoxicity in MMR-deficient CRC cells, little is known regarding the effect of MMR deficiency on trifluridine cytotoxicity in CRC.

AIM: We investigated whether trifluridine induces cytotoxicity in a DNA MMR-dependent manner and evaluated how truncated MBD4 alters trifluridine cytotoxicity.

METHODS: We utilized the human CRC cell lines HCT116 (hMLH1-deficient cells) and HCT116+ch3 (hMLH1-restored cells) and compared their sensitivities to trifluridine. And we established 5-fluorouracil-refractory hMLH1-deficient cells and analyzed trifluridine cytotoxicity. Finally, we established truncated MBD4 overexpressed CRC cell lines, and compared trifluridine sensitivity.

Keywords: MBD4; colorectal cancer; frameshift mutation; microsatellite instability; trifluridine

Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

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