Prevention of irradiation-induced salivary hypofunction by rapamycin in swine parotid glands

Oncotarget. 2016 Apr 12;7(15):20271-81. doi: 10.18632/oncotarget.7941.

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.

Keywords: mTOR; miniature pig; radiotherapy; rapamycin; salivary hypofunction.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cells, Cultured
  • Male
  • Parotid Gland / drug effects*
  • Parotid Gland / pathology
  • Parotid Gland / radiation effects
  • Salivary Glands / drug effects*
  • Salivary Glands / pathology
  • Salivary Glands / radiation effects
  • Sirolimus / pharmacology*
  • Submandibular Gland / drug effects*
  • Submandibular Gland / pathology
  • Submandibular Gland / radiation effects
  • Swine

Substances

  • Antibiotics, Antineoplastic
  • Sirolimus