Document Detail


Tyrosine Kinase Inhibitor PTK/ZK Enhances the Antitumor Effects of Interferon-α/5-Fluorouracil Therapy for Hepatocellular Carcinoma Cells.
MedLine Citation:
PMID:  20811948     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PURPOSE: There is no standardized treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus. We previously reported the efficacy of interferon-alpha and 5-fluorouracil combination (IFN/5-FU) therapy for these patients and the potential mechanism via the regulation of vascular endothelial growth factor (VEGF). In this study, we showed the VEGF-related effects of IFN/5-FU therapy using VEGF-receptor (VEGFR) selective inhibitor, PTK787/ZK222584 (PTK/ZK), in HCC cells.
METHODS: Using two VEGF secreting and VEGFR expressing human HCC cell lines, PLC/PRF/5 and HuH7, we performed growth inhibitory assays in vitro and in vivo, apoptosis assay, cell cycle analysis, and Western blot analysis for the mechanism, with or without PTK/ZK in IFN/5-FU therapy.
RESULTS: The combination of PTK/ZK and IFN/5-FU significantly inhibited cell growth in vitro and tended to reduce tumor growth in vivo in a HuH7 xenograft model in nude mice-in both cases without affecting VEGF secretion. PTK/ZK enhanced the IFN/5-FU induced apoptosis, based on increased proteins levels of Bax and reduced Bcl-xL and Bcl-2. Cell cycle analysis showed different results between the HCC cell lines following the combination therapy, possibly due to differences in p21 protein.
CONCLUSIONS: VEGF signaling inhibition would support an antitumor effect of IFN/5-FU therapy against HCC cell lines via induction of apoptosis and cell cycle delay.
Authors:
Masahiro Murakami; Shogo Kobayashi; Shigeru Marubashi; Yoshito Tomimaru; Takehiro Noda; Hiroshi Wada; Hidetoshi Eguchi; Yutaka Takeda; Masahiro Tanemura; Koji Umeshita; Yuichiro Doki; Masaki Mori; Hiroaki Nagano
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Publication Detail:
Type:  Journal Article     Date:  2010-09-02
Journal Detail:
Title:  Annals of surgical oncology     Volume:  18     ISSN:  1534-4681     ISO Abbreviation:  Ann. Surg. Oncol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9420840     Medline TA:  Ann Surg Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  589-96     Citation Subset:  IM    
Affiliation:
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
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