Effect of a novel orally bioavailable CXCR4 inhibitor, AMD070, on the metastasis of oral cancer cells

We have previously demonstrated that the stromal cell-derived factor (SDF-1)/CXCR4 system is involved in the metastasis of head and neck cancer. Additionally, it has been revealed that the blockade of CXCR4 by subcutaneous daily injection with AMD3100, a CXCR4 antagonist, may be effective in preventing metastasis in CXCR4-related head and neck cancer. Recent investigations have suggested that AMD070, a novel orally bioavailable inhibitor of CXCR4, may be minimally invasive compared with AMD3100. In the present study, we examined the effect of AMD070 on metastasis induced by the SDF-1/CXCR4 axis in B88-SDF-1 oral cancer cells, which express high levels of SDF-1 and CXCR4. Although treatment with AMD070 did not affect the anchorage-dependent growth of B88-SDF-1 cells, it significantly suppressed the anchorage-independent growth. Moreover, the SDF-1/CXCR4-dependent migration and invasion of B88-SDF-1 cells was significantly inhibited following treatment with AMD070. Subsequently, we performed an experimental therapy using AMD070 to prevent the distant metastasis of B88-SDF-1 cells in vivo. Daily oral administration of AMD070 significantly inhibited the lung metastasis of B88-SDF-1 cells in nude mice. These results indicated that AMD070 could be useful as a novel orally bioavailable inhibitor of oral cancer metastasis.