title: Prevention of irradiation-induced salivary hypofunction by rapamycin in swine parotid glands.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Baoxing
authors.initials: B
authors.lastname: Pang
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20852, USA.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Iglesias-Bartolome
authors.affiliation: 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.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA.
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.affiliation: 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.
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D008297:Male; D010306:Parotid Gland / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D012469:Salivary Glands / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D020123:Sirolimus / Q000494:pharmacology*; D013363:Submandibular Gland / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D013552:Swine
chemical_list: D000903:Antibiotics, Antineoplastic; D020123:Sirolimus
keywords: mTOR; miniature pig; radiotherapy; rapamycin; salivary hypofunction