Overexpression of Asparagine Synthetase and Matrix Metalloproteinase 19 Confers Cisplatin Sensitivity in Nasopharyngeal Carcinoma Cells

Abstract

Platinum-based concurrent chemoradiotherapy is considered a standard treatment approach for locoregionally advanced nasopharyngeal carcinoma. However, only a minority of patients benefit from this treatment regimen compared with radiotherapy alone. Identification of a set of molecular markers predicting sensitivity of platinum-based chemotherapy may contribute to personalized treatment of patients with nasopharyngeal carcinoma for better clinical outcome with less toxicity. Previously, we generated a cisplatin-sensitive nasopharyngeal carcinoma cell line, S16, by clonal selection from CNE-2 cells and found that eIF3a is upregulated and contributes to cisplatin sensitivity by downregulating the synthesis of nucleotide excision repair proteins. In this study, we conducted a gene expression profiling analysis and found three other genes, asparagine synthetase (ASNS), choriogonadotropin α subunit (CGA), and matrix metalloproteinase 19 (MMP19), that are upregulated in the cisplatin-sensitive S16 cells compared with the CNE-2 cells. However, only ASNS and MMP19, but not CGA, contributes to cisplatin sensitivity by potentiating cisplatin-induced DNA damage and apoptosis. Thus, ASNS and MMP19, along with eIF3a, are the sensitivity factors for cisplatin treatment and may serve as potential candidate molecular markers for predicting cisplatin sensitivity of advanced nasopharyngeal carcinoma.