RRC ID 52691
Author Kawamoto M, Umebayashi M, Tanaka H, Koya N, Nakagawa S, Kawabe K, Onishi H, Nakamura M, Morisaki T.
Title Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.
Journal Anticancer Res.
Abstract 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.
Volume 38(5)
Pages 2739-2748
Published 2018-5
DOI 10.21873/anticanres.12516
PII 38/5/2739
PMID 29715094
MeSH Aldehyde Dehydrogenase / biosynthesis Aldehyde Dehydrogenase / genetics Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Bile Duct Neoplasms / drug therapy* Bile Duct Neoplasms / metabolism Biomarkers, Tumor Cell Line, Tumor Cell Transdifferentiation / drug effects Cholangiocarcinoma / drug therapy* Cholangiocarcinoma / metabolism Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Humans Male Metronidazole / administration & dosage Middle Aged Neoplasm Invasiveness Neoplasm Proteins / biosynthesis Neoplasm Proteins / genetics Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / enzymology Spheroids, Cellular / drug effects
IF 1.865
Human and Animal Cells TFK-1(RCB2537)