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

Abstract

Platinum-based concurrent chemo-radiotherapy is considered a standard treatment approach for locoregionally advanced nasopharyngeal carcinoma (NPC). However, only a minority of patients benefit from this treatment regimen compared to radiotherapy alone. Identification of a set of molecular markers predicting sensitivity of platinum-based chemotherapy may contribute to personalized treatment of NPC patients for better clinical outcome with less toxicity. Previously, we generated a cisplain sensitive NPC cell line, S16, by clonal selection from CNE-2 cells and found that eIF3a is up-regulated and contributes to cisplatin sensitivity by down-regulating the synthesis of NER 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 up-regulated 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 sensitivity factors for cisplatin treatment and may serve as potential candidate molecular markers for predicting cisplatin sensitivity of advanced nasopharyngeal carcinoma.

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

“…22 In the present study, BST2 was identified as a platinum-resistant factor in NPC. Upregulation of BST2 resulted in platinum resistance by activating the NF- κ B pathway to promote the expression of anti-apoptotic proteins.…”

XPA expression is a predictive marker of the effectiveness of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

“…Although platinum-based chemotherapy often has good initial efficacy, cancer cells may acquire resistance to this therapy. Some of the potential mechanisms of resistance are reduced intracellular accumulation of cisplatin (29)(30)(31), inactivation of apoptotic pathways (32), increased DNA damage repair capacity (18,33), increased detoxification of cisplatin (34), and other epigenetic changes occurring at the molecular and cellular levels (35,36). Among these, NER, which mediates DNA damage repair, is believed to be one the most crucial determinants (18).…”

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

“…The threshold cycle (Ct) values were determined and normalized against that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) internal control. The relative mRNA levels were shown as the value of 2 −ΔCt against the control group [24]. …”

“…Western blotting was performed as described previously [24, 25]. Briefly, cell pellets were lysed in RIPA lysis buffer (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) followed by centrifugation to remove insoluble materials.…”