title: Interleukin-8 is related to poor chemotherapeutic response and tumourigenicity in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 133-713, Republic of Korea; Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 133-713, Republic of Korea.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Han
authors.affiliation: Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Jong Bin
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Man-Gil
authors.initials: MG
authors.lastname: Yang
authors.affiliation: Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 133-713, Republic of Korea.
authors.forename: Hee-Joung
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 133-713, Republic of Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: An
authors.affiliation: Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 133-713, Republic of Korea. Electronic address: jhkim@korea.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology; D034622:RNA Interference; D053700:Receptors, Interleukin-8 / Q000378:metabolism; D058985:Side-Population Cells / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D016209:Interleukin-8; D053700:Receptors, Interleukin-8; D004317:Doxorubicin; D017239:Paclitaxel
keywords: ATP-binding cassette transporter; Drug resistance; Hepatocellular carcinoma; IL-8; Side population