Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation

作者：Morgan Bathke Maria; Hill Grace A; Harris Zoey I; Lin Her H; Chibly Alex M; Klein Rob R; Burd Randy; Ann David K; Limesand Kirsten H^*

来源：Scientific Reports, 2014, 4(1): 5206.

DOI：10.1038/srep05206

The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f); Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6-8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f); Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer.

• 出版日期2014-6-6