Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model

Cho,Kang  Su; Yoon,So   Jung; Lee,Joo   Yong; Cho,Nam   Hoon; Choi,Young   Deuk; Song,Yun   Seob; Hong,Sung   Joon

doi:10.3892/ol.2013.1515

Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model

Authors:
- Kang Su Cho
- So Jung Yoon
- Joo Yong Lee
- Nam Hoon Cho
- Young Deuk Choi
- Yun Seob Song
- Sung Joon Hong
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Affiliations: Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, Department of Urology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul 140-743, Republic of Korea
Published online on: August 6, 2013 https://doi.org/10.3892/ol.2013.1515
Pages: 933-938

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Abstract

The stromal derived factor‑1 (SDF‑1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF‑1 and a CXCR4‑specific antagonist, AMD3100, on human prostate cancer PC‑3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC‑3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100‑treated and untreated groups. Cell proliferation was not significantly affected by SDF‑1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF‑1 stimulation enhanced the expression of phosphorylated Akt in the PC‑3 cells, but that the SDF‑1‑induced expression of phosphorylated Akt was abrogated in the AMD3100‑treated PC‑3 cells. In the PC‑3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100‑treated PC‑3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki‑67 and the anti‑apoptotic marker Bcl‑2 compared to control tumors in vivo. The CXCR4‑specific antagonist inhibits SDF‑1‑induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC‑3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration‑resistant prostate cancer (CRPC).

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