Adenoid cystic carcinoma (ACC) is a highly malignant carcinoma characterized by local invasion and a high incidence of distant metastasis.In the present study, we used high (ACCM) and low (ACC2) metastasis cell lines of human ACC as an experimental model to study metastatic mechanisms and compare their expression levels of the angiogenic related factor vascular endothelial growth factor (VEGF).Bio-Plex analysis of 26 different cytokines was performed in order to determine the protein profiles under hypoxia (2％ O2) of two ACC cell lines.In these cytokines, the signal ratios of VEGF protein levels showed a high ratio in their relative intensities of hypoxic versus normoxic signals.A typical transcriptional factor activated by hypoxia, hypoxia-inducible factor-1 (HIF-1), was induced, with significant increases observed in ACCM cells but not in ACC2 cells.HIF-1α predominantly regulates elevated vegfpromoter activities in ACCM cells but not in ACC2 cells, depending on the accessibility of its binding to hypoxia responsive elements (HREs) that mediate primarily the transcriptional response to cellular hypoxia on vegfpromotor.Furthermore, suppression of hypoxia-induced VEGF protein levels in ACCM cells by HIF-1α siRNA and/or a chemical inhibitor of HIF-1 was observed, suggesting that hypoxia-increased VEGF levels are HIF-1α-dependent.Taken together, these findings suggest that HIF-1α-dependent VEGF over-expression under hypoxic conditions shows associations with the metastatic tendencv of ACC cells to some extent and may function as a potential target for ACC therapy.