AMD3100 inhibits epithelial–mesenchymal transition, cell invasion, and metastasis in the liver and the lung through blocking the SDF‐1α/CXCR4 signaling pathway in prostate cancer

Abstract Stromal cell‐derived factor‐1 (SDF‐1) and CXC chemokine receptor 4 (CXCR4) have been found to be tightly correlated with the progression of prostate cancer (PC). In this study, we investigated the effects of an SDF‐1α/CXCR4 inhibitor, AMD3100, on cell progression and metastasis potential of human PC cells. Human PC cell lines (LNCaP, PC3, and DU145) were cultured to detect SDF‐1α/CXCR4, which showed higher SDF‐1α and CXCR4 expression than the normal human prostate epithelial cell line, RWPE‐1. AMD3100 was confirmed to be an inhibitor of SDF‐1α, and to detect the effect of SDF‐1α/CXCR4 inhibition on PC, PC cells were treated with AMD3100 or/and CXCR4 siRNA. The results suggested that inhibition of the SDF‐1α/CXCR4 pathway could promote the E‐cadherin level but inhibit the levels of invasion and migration of vimentin, N‐cadherin and α5β1 integrin. Finally, tumor formation in nude mice was conducted, and the cell experiment results were verfied. These data show that AMD3100 suppresses epithelial–mesenchymal transition and migration of PC cells by inhibiting the SDF‐1α/CXCR4 signaling pathway, which provides a clinical target in the treatment of PC.