title: Annexin A1 is involved in resistance to 5-FU in colon cancer cells.
abstract: Resistance to 5-fluorouracil (5‑FU), a key drug in the treatment of colorectal cancer, is one of the major reasons for poor patient prognosis during cancer treatment. Annexin A1 (ANXA1) is a calcium‑dependent phospholipid‑linked protein that is associated with drug resistance, anti‑inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. Although there have been several studies investigating ANXA1 expression in drug resistant cells, the role of ANXA1 is yet to be fully understood. We therefore, in this study, generated SW480 cells resistant to 5‑FU (SW480/5‑FU) to evaluate ANXA1 expression. When compared to the control cells, ANXA1 expression was significantly induced in the SW480/5‑FU cells. We then revealed the role of ANXA1 expression in 5‑FU resistance by using overexpression and knockdown methods in colon cancer cells. Overexpression of ANXA1 induced a significant increase of cell viability to 5‑FU, whereas ANXA1 knockdown induced a significant decrease of cell viability to 5‑FU. Further experiments revealed that ANXA1 expression was induced by hypoxia in colon cancer cells. These results suggest that ANXA1 expression may play a critical role in 5‑FU resistance and may be induced by hypoxia during cancer progression. Our results provide a possible strategy to overcome 5‑FU resistance by modulating ANXA1 expression.
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Onozawa
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kanke
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Hayase
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Ishigame
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Momma
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohki
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
mesh_terms: D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D000072258:Tumor Hypoxia / Q000235:genetics
chemical_list: D017305:Annexin A1; D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil