Wu Haiwei, Huang Shengyun, Chen Zhanwei, Liu Wenlei, Zhou Xiaoqing, Zhang Dongsheng
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6467-74. doi: 10.3892/mmr.2015.4255. Epub 2015 Aug 26.
Adenoid cystic carcinoma (ACC) is one of the most common types of salivary gland malignancy in the head and neck, and its aggressive ability to invade and metastasize is an important reason for its poor survival rates. Our previous investigations confirmed that autophagy‑associated gene expression is closely associated with the occurrence and development of ACC. On this basis, the present study further investigated hypoxia‑induced autophagy and its role in tumor invasion. Cobalt chloride (CoCl2) was used to mimic hypoxia. The results of the present study indicated that autophagosome formation and upregulation of autophagy‑associated microtubule‑associated protein 1 light chain 3 and Beclin 1 were observed in ACC‑M cells in response to CoCl2. The hypoxia‑inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K‑interacting protein 3 signaling pathway was involved in hypoxia‑induced autophagy in ACC. Furthermore, inhibition of autophagy by chloroquine markedly attenuated the tumor invasion induced by mimetic hypoxia in ACC. These results suggested that hypoxia‑induced autophagy may serve as a potential target for the future treatment of ACC.
腺样囊性癌(ACC)是头颈部最常见的涎腺恶性肿瘤类型之一,其侵袭和转移的侵袭性能力是其生存率低的重要原因。我们之前的研究证实,自噬相关基因表达与ACC的发生发展密切相关。在此基础上,本研究进一步探讨了缺氧诱导的自噬及其在肿瘤侵袭中的作用。使用氯化钴(CoCl2)模拟缺氧。本研究结果表明,在ACC-M细胞中,对CoCl2的反应观察到自噬体形成以及自噬相关微管相关蛋白1轻链3和Beclin 1的上调。缺氧诱导因子1α/B细胞淋巴瘤2/腺病毒E1B 19K相互作用蛋白3信号通路参与了ACC中缺氧诱导的自噬。此外,氯喹抑制自噬显著减弱了模拟缺氧诱导的ACC肿瘤侵袭。这些结果表明,缺氧诱导的自噬可能成为未来ACC治疗的潜在靶点。