Abstract
Irradiation can cause salivary gland hypofunction, with hyposalivation producing discomfort, health risks, and reducing function in daily life. Despite increasing translational research interest in radioprotection, there are no satisfactory treatments available. Keratinocyte growth factor-1 stimulates proliferation of salivary epithelial cells or salivary stem/progenitor cells. However, the exact mechanism of its radioprotection against radiation-induced salivary hypofunction is not fully elucidated. Our results reveal that the radioprotective effects of keratinocyte growth factor-1 involved alleviation of growth inhibition and anti-apoptotic cell death of human parotid epithelial cells. Furthermore, keratinocyte growth factor-1 protected human parotid epithelial cells through the phosphoinositide 3-kinase – protein kinase B (Akt) pathway and inhibition of p53-mediated apoptosis through activation of mouse double minute 2. Local delivery of keratinocyte growth factor-1 into the irradiated salivary glands could protect radiation-induced salivary cell damages, suppress p53-mediated apoptosis and prevent salivary hypofunction in vivo. This suggests that keratinocyte growth factor-1 is a promising candidate to prevent radiation-induced salivary hypofunction and raise rational development keratinocyte growth factor-1 local delivery system.
Highlights
Radiotherapy is the main treatment in patients with head and neck cancer
Our results indicate for the first time that KGF-1 can provide radioprotection to salivary gland (SG) epithelial cells by reducing DNA damage and p53-mediated apoptosis following irradiation, in which phosphoinositide 3-kinase (PI3K)- protein kinase B (Akt)-p53 pathway mediates the radioprotective effect of KGF-1
We initially investigated irradiation response of human parotid epithelial cells in vitro to examine the mechanisms of KGF-1 on radioprotection of salivary epithelial cells
Summary
Due to the structural proximity and complexity in head and neck area, irradiation-induced salivary gland (SG) damage is common. Hyposalivationrelated complications such as xerostomia, halitosis, burning sensation, bizarre taste, swallowing difficulty and dental caries decrease the quality of life [1]. An increasing number of studies using bioactive factors for prevention or amelioration of irradiation-induced SG damage have been conducted [3,4,5,6]. Keratinocyte growth factor-1 (KGF-1, known as FGF-7) stimulates the growth of epithelial cells and protects those cells from chemotherapy or radiotherapy-induced oral mucositis. KGF-1 has potential for amelioration of irradiation-induced salivary hypofunction [5, 6]
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