Autophagy: a new target for the treatment of salivary gland adenoid cystic carcinoma

Abstract

BACKGROUND: Our previous studies found that expression of Beclin 1 and other autophagy related genes in salivary gland adenoid cystic carcinoma (ACC) was lower than tumour-adjacent normal tissue. Beclin 1 protein and mRNA expression were independent prognostic factors for ACC patients. We hypothesized that autophagy may influence chemosensitivity and radiosensitivity of ACC. OBJECTIVES: To investigate the role of autophagy in radiotherapy and chemotherapy of salivary gland ACC. METHODS: The autophagy level and the expression of Beclin 1 were investigated when ACC cells treated with Obatoclax, Cisplatin, radiation, or Cisplatin+ radiation. Then the cytotoxicity was evaluated when down-regulating or up-regulating expression of Beclin 1, with or without pharmacologically inhibiting autophagy level or apoptosis activity. FINDINGS: Obatoclax increased autophagy level and expression of Beclin 1 in ACC cells. These effects were suppressed by 3-MA or CQ. Autophagy level was decreased when suppressing Beclin 1 expression. When autophagy was suppressed by Beclin 1 shRNA, 3-MA or CQ, sensitivity to Cisplatin of ACC cells was significantly increased. However radiosensitivity of cells decreased when autophagy was suppressed. CONCLUSIONS: Autophagy participates in responding to chemotherapy and radiation of human salivary gland ACC cells. Regulation of autophagy level can influence chemosensitivity and radiosensitivity of ACC cells. These findings indicated regulating of autophagy would be a new therapeutic strategy for salivary gland ACC. The project was supported by Seed Funding Programme for Basic Research, the University of Hong Kong (No. 201501159006).