Tohoku J. Exp. Med., 2012 Oct, 228(2)

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

XIN LIU,¹ JING PENG,² WENCHANG SUN,¹ SHUFENG YANG,¹ GUOYING DENG,¹ FANG LI,² JYA-WEI CHENG³ and JOHN R. GORDON⁴

¹Department of Microbiology, Dalian Medical University, Dalian, P.R. China
²Department of Immunology, Dalian Medical University, Dalian, P.R. China
³Institute of Biotechnology, Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan
⁴The Division of Respirology, Critical Care and Sleep Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada

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.

keywords —— chemokine; CXCR1; CXCR2; G31P; prostate cancer

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 228, 147-156

Correspondence: Fang Li, Department of Immunology, Dalian Medical University, 9 Western Lüshun South Road, Dalian, P.R. China.

e-mail: lifang16@hotmail.com