Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation

Int J Cancer. 2004 Sep 10;111(4):508-13. doi: 10.1002/ijc.20286.


In vitro, the human prostate cancer (PCA) cell line LNCaP can be permanently transdifferentiated into a quiescent neuroendocrine (NE) phenotype by the cytokine interleukin-6 (IL-6). Recently, we have shown that the growth of prostate cancer cells is significantly suppressed when cocultured with NE cells. In order to explore the inhibitory activity of IL-6 on prostate tumor growth, nude mice bearing xenografts of the PCA cell lines LNCaP and DU-145 (a line that is incapable of NE transdifferentiation by IL-6 in vitro) were treated with IL-6 for 3 weeks, either injected around the tumor or systematically released from implanted minipumps. Both administration forms of IL-6 inhibited the growth of LNCaP xenografts by more than 75% compared to the control group. In contrast, there was no difference in DU-145 tumor growth between IL-6-treated animals and controls. In comparison to control and DU-145 tumors, both IL-6 injected and pump-infused LNCaP tumors exhibited a significant increase in the expression of the NE markers neuron-specific enolase (NSE) and betaIII tubulin. Serum NSE levels were also significantly elevated in both IL-6-treated LNCaP tumor groups when compared to controls. IL-6 treatment resulted in G(0) cell cycle accumulation as evidenced by a loss of Ki-67 expression in > 90% of LNCaP tumor cells. These combined results demonstrate that IL-6-induced NE transdifferentiation of PCA cells has a significant inhibitory effect on tumor growth in mice. Agents, like IL-6, capable of NE transdifferentiation of PCA cells, should be considered as a new therapeutic approach for the treatment of prostate cancer.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation / drug effects*
  • Disease Progression
  • Humans
  • Interleukin-6 / pharmacology*
  • Ki-67 Antigen / biosynthesis
  • Male
  • Mice
  • Mice, Nude
  • Neurosecretory Systems / physiology
  • Phenotype
  • Phosphopyruvate Hydratase / analysis
  • Prostatic Neoplasms / physiopathology*
  • Prostatic Neoplasms / veterinary
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Interleukin-6
  • Ki-67 Antigen
  • Phosphopyruvate Hydratase