Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells

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

研究成果: Contribution to journalArticle査読

18 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)589-596
ページ数8
ジャーナルAnnals of Surgical Oncology
18
2
DOI
出版ステータス出版済み - 2 2011

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

フィンガープリント 「Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル