Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328

Hannes Steiner, Ilaria T. Cavarretta, Patrizia L. Moser, Andreas P. Berger, Jasmin Bektic, Hermann Dietrich, Mohamed H. Zaki, Marian Nakada, Alfred Hobisch, Jeffrey A. Nemeth, Zoran Culig

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Interleukin-6 (IL-6) is a multifunctional regulator of cellular events in prostate cancer. LNCaP-IL-6+ cells selected in the presence of IL-6 were taken for assessment of effects of the chimeric monoclonal anti-IL-6 antibody CNTO 328. METHODS. Cell viability was assessed after treatment with CNTO 328 by the ATP assay. Expression of Bcl-2 and Bax and activation of signaling pathways were evaluated by Western analysis. Nude mice were inoculated with LNCaP-IL-6+ cells and treated with CNTO 328. The tumors were analyzed by immunohistochemistry for expression of Ki-67, tissue transglutaminase, and vascular endothelial growth factor. RESULTS. CNTO 328 caused a statistically significant inhibition of cell viability. The protein levels of Bcl-2 and the phosphorylation of ERK1/2 mitogen-activated protein kinases were decreased by the anti-IL-6 antibody. Treatment with CNTO 328 yielded an increase in the phosphorylation of signal transducers and activators of transcription factor 3. The mean tumor volume in animals inoculated with LNCaP-IL-6+ cells and treated with CNTO 328 was insignificantly lower than that in animals treated with the control antibody. There was a statistically significant decrease in the percentage of Ki-67-positive cells in CNTO 328-treated tumors. CONCLUSION. CNTO 328 has a potential in prostate cancer therapy and could be further tested in various combination experimental treatments.

Original languageEnglish
Pages (from-to)1744-1752
Number of pages9
JournalProstate
Volume66
Issue number16
DOIs
Publication statusPublished - Dec 1 2006

Keywords

  • Interleukin-6
  • Monoclonal antibody
  • Prostate tumor
  • Targeted therapy
  • Xenografts

ASJC Scopus subject areas

  • Urology

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