title: Vitamin K2 has growth inhibition effect against hepatocellular carcinoma cell lines but does not enhance anti-tumor effect of combination treatment of interferon-alpha and fluorouracil in vitro.
abstract: Several studies have recently reported the efficacy of combination therapy of interferon (IFN) alpha and 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). However, the clinical effect of this treatment was not complete. The new therapeutic modality should be necessary to rise up this clinical response rate. Recently, the anti-tumor effect of Vitamin K2 has been reported in terms of decreased recurrence rate of HCC patients. The aim of this study was to explore the additive or synergistic effect of Vitamin K2 to combined therapy of interferon (IFN) alpha and 5-fluorouracil (5-FU) against hepatocellular carcinoma (HCCs). The study was conducted using three hepatoma cell lines (PLC/PRF/5, Hep3B and HepG2). The 3-(4-5-dimethylthiazol-2-yl)-2, 5-dyphenyl tetrazolium bromide (MTT) assay (48h) revealed anti-tumor effect of IFNalpha and 5-FU. Cell growth assay (3-7 days) showed growth inhibitory effect of Vitamin K2 on three cell lines after day 5. But additional effect of combination treatment of Vitamin K2 and IFNalpha/5-FU was not observed in any time course from 48h to 7 days. Cell cycles were assessed with flowcytometry. Although either Vitamin K2 or IFNalpha/5-FU alone has the influence to the cell cycles, no significant change was shown in the combination of Vitamin K2 and IFNalpha/5-FU. In conclusion, Vitamin K2 itself has potentially growth inhibitory effect for HCC cell lines, but does not enhance the anti-tumor effect of IFNalpha and 5-FU.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, 565-0871 Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroaki
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authors.lastname: Nagano
authors.forename: Takehiro
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authors.lastname: Noda
authors.forename: Hiroshi
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authors.lastname: Wada
authors.forename: Hideo
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authors.lastname: Ota
authors.forename: Bazarragchaa
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authors.lastname: Damdinsuren
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
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authors.lastname: Miyamoto
authors.forename: Yutaka
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authors.lastname: Takeda
authors.forename: Yuichiro
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authors.lastname: Doki
authors.forename: Koji
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authors.lastname: Umeshita
authors.forename: Keizo
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authors.lastname: Dono
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Morito
authors.initials: M
authors.lastname: Monden