Combined gemcitabine and metronidazole is a promising therapeutic strategy for cancer stem-like cholangiocarcinoma

Makoto Kawamoto, Masayo Umebayashi, Hiroto Tanaka, Norihiro Koya, Sinichiro Nakagawa, Ken Kawabe, Hideya Onishi, Masafumi Nakamura, Takashi Morisaki

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

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Background/Aim: Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). Materials and Methods: We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. Results: MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). Conclusion: MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA.

本文言語英語
ページ(範囲)2739-2748
ページ数10
ジャーナルAnticancer research
38
5
DOI
出版ステータス出版済み - 5 2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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