Zhu Zhao, Pang Baoxing, Iglesias-Bartolome Ramiro, Wu Xiaoshan, Hu Lei, Zhang Chunmei, Wang Jinsong, Gutkind J Silvio, Wang Songlin
Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China.
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20852, USA.
Oncotarget. 2016 Apr 12;7(15):20271-81. doi: 10.18632/oncotarget.7941.
Radiotherapy is commonly used in patients with oral cavity and pharyngeal cancers, usually resulting in irreversible salivary hypofunction. Currently management of radiation damage to salivary glands still remains a great challenge. Recent studies show that activation of mammalian target of rapamycin (mTOR) occurs in salivary gland lesions, making it possible to apply mTOR inhibitor for treatment. Our results indicate inhibition of mTOR by rapamycin significantly alleviated irradiation-induced salivary hypofunction by restoring 46% salivary flow rate and protecting histological structures in swine. Furthermore, rapamycin protected human submandibular gland cell line (HSG) from irradiation-induced cell depletion and loss of cell proliferation capacity. These findings lay the foundation for a new clinical application of rapamycin to prevent irradiation-induced salivary hypofunction.
放射疗法常用于口腔和咽喉癌患者，通常会导致不可逆的唾液腺功能减退。目前，唾液腺辐射损伤的管理仍然是一个巨大的挑战。最近的研究表明，雷帕霉素靶蛋白（mTOR）在唾液腺病变中被激活，这使得应用mTOR抑制剂进行治疗成为可能。我们的结果表明，雷帕霉素抑制mTOR可显著减轻辐射诱导的唾液腺功能减退，使猪的唾液流速恢复46%，并保护其组织结构。此外，雷帕霉素可保护人下颌下腺细胞系（HSG）免受辐射诱导的细胞耗竭和细胞增殖能力丧失的影响。这些发现为雷帕霉素预防辐射诱导的唾液腺功能减退的新临床应用奠定了基础。
