Interleukin-8 is related to poor chemotherapeutic response and tumourigenicity in hepatocellular carcinoma

Seo Young Park, Jiyou Han, Jong Bin Kim, Man Gil Yang, Yoon Jun Kim, Hee Joung Lim, Su Yeon An, Jong Hoon Kim

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aim Interleukin-8 (IL-8) has been suggested as a prognostic biomarker for human hepatocellular carcinoma (HCC), but its roles in HCC progression and drug resistance have not been studied. This study investigates the role and underlying mechanism of IL-8 in the chemoresistance and progressive growth of HCC. Methods The change of chemosensitivity and proportion of side population in hepatoma cells was examined by cell growth and flow cytometric analyses after anti-cancer treatments or knockdown of IL-8. Expression of IL-8 and ATP-binding cassette (ABC) transporters in hepatoma cells, xenograft and clinical HCC tissues was determined by Western blot and immunohistochemical analyses. Tumourigenicity of hepatoma cells was evaluated in vivo after silencing IL-8 gene. Results Treatment of hepatoma cells with anti-cancer drugs increased the production of IL-8 and its receptor, as well as the proportion of side population (SP). Exogenous IL-8 increased the SP fraction and expression of multidrug resistance-1, decreasing the drug sensitivity. Silencing of IL-8 gene decreased the ratio of SP cells and drug resistance properties. Both IL-8 and ABC transporters were highly expressed in xenograft and clinical HCC tissues, and knockdown of IL-8 significantly reduced tumour size in vivo. Conclusion Anti-cancer drug-induced IL-8 secretion increased the expression of ABC transporters and SP cells, promoting the growth of HCC in vitro. Thus IL-8 may be a potential therapeutic target in the treatment of HCC.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalEuropean Journal of Cancer
Volume50
Issue number2
DOIs
Publication statusPublished - 2014 Jan

Keywords

  • ATP-binding cassette transporter
  • Drug resistance
  • Hepatocellular carcinoma
  • IL-8
  • Side population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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