Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)TRAIL receptor pathway to antitumor effects of interferon-α/5-fluorouracil against hepatocellular carcinoma

Tameyoshi Yamamoto, Hiroaki Nagano, Masato Sakon, Hisashi Wada, Hidetoshi Eguchi, Motoi Kondo, Bazarragchaa Damdinsuren, Hideo Ota, Masato Nakamura, Hiroshi Wada, Shigeru Marubashi, Atsushi Miyamoto, Keizo Dono, Koji Umeshita, Shoji Nakamori, Hideo Yagita, Morito Monden

研究成果: Contribution to journalArticle査読

68 被引用数 (Scopus)

抄録

Purpose: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNα and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). Experimental Design: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNα, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNα-induced cytotoxic effects of PBMC on HCC cell lines were examined by 51Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. Results: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNα induced TRAIL on CD4+ T cells, CD14+ monocytes, and CD56+ NK cells. Treatment of effector cells by IFNα and target HCC cells by 5-FU enhanced the cytotoxicity of CD14+ monocytes and CD56+ NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNα/5-FU combination therapy, and TRAIL+ mononuclear cells were found in cancer tissue of a responder. Conclusion: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNα and 5-FU combination therapy.

本文言語英語
ページ(範囲)7884-7895
ページ数12
ジャーナルClinical Cancer Research
10
23
DOI
出版ステータス出版済み - 12 1 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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「Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)TRAIL receptor pathway to antitumor effects of interferon-α/5-fluorouracil against hepatocellular carcinoma」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。

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