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

• Published in: Oncology reports Vol. 40; no. 1; pp. 303 - 308
• Main Authors: Uchida, Daisuke, Kuribayashi, Nobuyuki, Kinouchi, Makoto, Sawatani, Yuta, Shimura, Michiko, Mori, Toshimitsu, Hasegawa, Tomonori, Miyamoto, Youji, Kawamata, Hitoshi
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01-07-2018; Spandidos Publications UK Ltd
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Cancer metastasis; Cancer therapies; Care and treatment; Cell Line, Tumor; Chemokines; Chemotherapy; Complications and side effects; Genetic aspects; Health aspects; Heterocyclic Compounds, 1-Ring - administration & dosage; Heterocyclic Compounds, 1-Ring - adverse effects; HIV; Human immunodeficiency virus; Humans; Laboratory animals; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lymphatic system; Metastasis; Mice; Mouth cancer; Mouth Neoplasms - drug therapy; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Neoplasm Metastasis; Oral cancer; Pancreatic cancer; Pathogens; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - genetics; Studies; Xenograft Model Antitumor Assays; United States > US; Japan
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2018.6400

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.