G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

DOI Web Site PubMed 参考文献80件
  • Liu Xin
    Department of Microbiology, Dalian Medical University
  • Peng Jing
    Department of Immunology, Dalian Medical University
  • Sun Wenchang
    Department of Microbiology, Dalian Medical University
  • Yang Shufeng
    Department of Microbiology, Dalian Medical University
  • Deng Guoying
    Department of Microbiology, Dalian Medical University
  • Li Fang
    Department of Immunology, Dalian Medical University
  • Cheng Jya-Wei
    Institute of Biotechnology, Department of Life Science, National Tsing Hua University
  • Gordon John R.
    The Division of Respirology, Critical Care and Sleep Medicine, Royal University Hospital, University of Saskatchewan

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Prostate cancer is the most common malignancy in Western countries. Chemokine C-X-C motif receptor 1 (CXCR1) and CXCR2 play a key role in generation and regulation of CXC chemokine signaling. CXCR1 is a receptor for interleukin 8 (IL8), a pro-inflammatory chemokine, and CXCR1/2 are crucially involved in the prostate cancer development and progression. Thus, we generated a high-affinity human CXCR1/CXCR2 inhibitor, CXCL8 (3-72) K11R/G31P, named G31P, which is a synthetic derivative of the human cytokine, IL-8. In this study, we investigated the effects of G31P on regulation of prostate cancer cell growth in vitro and in nude mouse xenografts. Cell viability, adhesion, and wound healing assays were used to assess the effects of G31P on growth, adhesion, and migration of PC-3 human prostate cancer cells in vitro, respectively. Nude mouse xenografts and xenograft implantation assays were performed to determine the effect of G31P on PC-3 cells in vivo. Immunohistochemistry was used to detect gene expression, and fluorescence imaging was used to detect tumor volume and microvessel density in tumor xenografts. The data showed that G31P treatment significantly reduced PC-3 cell viability, adhesion and migration capacity in a dose-dependent manner (up to 100 ng/ml). Additionally, G31P treatment of nude mice suppressed the growth of orthotopically transplanted tumor xenografts. G31P also inhibited tumor tissue vascularization, which was associated with the decreased expression of vascular endothelial growth factor and nuclear transcription factor (NF)-κB in orthotopic xenograft tissues. This study provides evidence that G31P, a CXCR1/2 inhibitor, may effectively control prostate cancer.

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