Prevention of irradiation-induced salivary hypofunction by rapamycin in swine parotid glands
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Zhao Zhu1, Baoxing Pang1, Ramiro Iglesias-Bartolome2, Xiaoshan Wu1, Lei Hu1, Chunmei Zhang1, Jinsong Wang1, J. Silvio Gutkind3, Songlin Wang1
1Molecular 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
2Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20852, USA
3Department of Pharmacology and Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA
Songlin Wang, e-mail: [email protected]
J. Silvio Gutkind, e-mail: [email protected]
Keywords: radiotherapy, salivary hypofunction, miniature pig, rapamycin, mTOR
Received: November 21, 2015 Accepted: February 09, 2016 Published: March 06, 2016
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.
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