Combination of Pan-HDAC Inhibitor and COX-2 Inhibitor Produces Synergistic Anticancer Effects in Human Salivary Adenoid Cystic Cancer Cells

Objective: To evaluate whether the combination of the pan-histone deacetylase (HDAC) inhibitor, suberanilohydroxamic acid (SAHA), and the cyclooxygenase-2 (COX-2) inhibitor, celecoxib, could produce synergistic anticancer effects in human salivary adenoid cystic cancer (SACC) cells. Methods: SACC cells were treated with the COX-2 inhibitor celecoxib or the pan-HDAC inhibitor SAHA, or a combination of celecoxib and SAHA, for 24 hours. Cell proliferation, apoptosis, migration and invasion were evaluated using the cell counting kit 8 (CCK-8) assay, and the 4',6-diamidino-2-phenylindole staining assay, transwell migration or invasion assays, respectively. The protein expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and protein kinase B or AKT1(PKB/AKT) were evaluated using western blot. Results: The combinational treatment with SAHA and celecoxib synergistically inhibited cell proliferation, migration and invasion, and synergistically induced apoptosis, whereas the treatment with SAHA or celecoxib alone only slightly inhibited cell proliferation, migration and invasion, and slightly induced apoptosis. Meanwhile, the combinational treatment synergistically upregulated the membrane-bound PTEN (activated form) and downregulated phospho-AKT (activated form). Conclusion: The combination of pan-HDAC and COX-2 inhibitors produced synergistic anticancer effects at least partially via activating PTEN and inactivating AKT in the SACC cells. Keywords: HDAC, COX-2, celecoxib, SACC, SAHA