title: Synergistic antitumor effect of interferon-ß with gemcitabine in interferon-α-non-responsive pancreatic cancer cells.
abstract: Interferon (IFN)-ß is reported to have more potent antitumor effects than IFN-α. The aim of this study was to compare the synergistic antitumor activity of both IFNs when combined with gemcitabine on cultured pancreatic cancer cells expressing various levels of IFN receptor. The growth-inhibitory effects of IFN-α and IFN-ß in combination with gemcitabine on three human pancreatic cancer cell lines (BxPC-3, MIAPaCa-2, Panc-1) were evaluated by MTT assay and isobolographic analysis. We also correlated their growth-inhibitory effects with the expression status of type I IFN receptor type 2 (IFNAR2). Western blot analysis indicated strong expression of IFNAR2 in BxPC-3 and MIAPaCa-2, but weak expression in Panc-1. The growth-inhibitory effect of gemcitabine was enhanced synergistically by IFN-α in BxPC-3 and MIAPaCa-2, but not in Panc-1. IFN-ß exhibited more potent synergistic growth-inhibitory effects with gemcitabine in BxPC-3 and MIAPaCa-2 compared to IFN-α, and also synergistic enhancement in Panc-1. In conclusion, our results indicated that the growth-inhibitory effect of IFN-ß with gemcitabine was synergistic not only in pancreatic cancer cells with strong expression of IFNAR2, but also in those with weak expression of IFNAR2.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Akira
authors.initials: A
authors.lastname: Tomokuni
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemura
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D000093542:Gemcitabine
chemical_list: C508033:IFNAR2 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D003841:Deoxycytidine; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D000093542:Gemcitabine