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Short palate, lung and nasal epithelium clone 1 (SPLUNC1) gene coded a secreted protein found at the surface of nasopharyngeal epithelium, which may be an important risk factor for nasopharyngeal carcinoma (NPC).Here we observed the effects of SPLUNC 1 and a bactericidal permeability-increasing protein deletion mutant on the cell biological behaviors and tumorigenicity of nasopharyngeal carcinoma HNE-1 cells.We analyzed the effects of SPLUNC 1 on proteins in the mitogen-activated protein kinase and NFκB pathways, detected its expression in cancerous and normal nasopharyngeal specimens and nasopharyngeal secretions by immunohistochemistry, western blot and ELISA.We found that SPLUNC 1 gene inhibits the malignant phenotype of the NPC cells, and stimulates NPC cell apoptosis via the receptor and mitochondrial pathways.SPLUNC1 expression was dramatically down regulated at early stage of NPC and in nasopharyngeal secretions from both the affected and unaffected tissues of NPC patients.This study suggesting that SPLUNC 1 protein can prevent the incidence of NPC at the early stages of NPC and be easily detected in the nasopharyngeal secretions, and can act as an early diagnosis marker for NPC.