Inhibitory effect of chidamide on the growth of human adenoid cystic carcinoma cells

Adenoid cystic carcinoma (ACC) is a malignant epithelial neoplasm that limitedly responses to chemotherapy at the cost of significant toxicity. There is no single targeted drug approved by Food and Drug Administration (FDA) for ACC. Genomic landscape studies have revealed that frequently mutated pathways in ACC often involve in chromatin remodeling, which interfere multiple histone related proteins. Chidamide is a novel histone deacetylase inhibitor (HDACi) approved in clinical practice that was designed to increase the acetylation level of histone H3. It demonstrated anticancer effects in various cancers in preclinical study, but not in ACC. In this study, we aimed to investigate the anticancer effects of chidamide alone or in combination with cisplatin (cDDP) on ACC in vitro and in vivo. The results showed that chidamide alone or in combination with cDDP effectively inhibited the growth and proliferation of ACC cells in a dose-and time-dependent manner. Chidamide arrested cell cycle in G2/M phase by up-regulating the acetylation of histone H3 and interfering phosphorylation of AKT protein. Chidamide alone or in combination with cDDP did not induce distinct apoptosis in ACC cells. In vivo experiments showed that chidamide combining cDDP exerted significant inhibitory effects on ACC. These suggest that chidamide may be a promising candidate drug for the treatment of patients with ACC.