P2-001 - The functional role of NGFR in regulating chemosensitivity in nasopharyngeal carcinoma

Abstract

Background: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in southern China. Induction chemotherapy and concurrent chemo-radiation are major treatment methods for advanced NPC patients. However, patients will develop resistant phenotype during treatment, leading to treatment failure and cancer recurrence. Nevertheless, how NPC acquires chemoresistance remains largely unknown. Nerve growth factor receptor (NGFR) is a neurotrophin receptor and expresses on the plasma membrane. We found that NGFR expression was up-regulated upon cisplatin treatment, which promotes us to investigate the regulatory role of NGFR in mediating cisplatin resistance in NPC. Methods: Real-time PCR, western blot, and immunocytochemistry staining were used to determine the expression level of NGFR in response to cisplatin treatment. In vivo mouse xenograft model was further used to validate the inducing effect in vitro. NGFR-specific shRNA was used to knockdown the expression of NGFR. In vitro toxicity test was performed to test the sensitivity of cells to cisplatin. Results: Cisplatin treatment induced the expression of NGFR in NPC cells. Cisplatin-resistant cells were developed by chronic cisplatin treatment. NGFR was significantly up-regulated in cisplatin-resistant cells. In mouse xenograft model, cisplatin treatment also promoted NGFR expression, which further confirmed the inducing effect in vitro. Knockdown of the expression of NGFR could significantly sensitize cisplatin-resistant NPC cells to cisplatin. Conclusion: Our results demonstrated that inducible NGFR expression mediated acquired resistance to cisplatin in NPC. Targeting NGFR might be clinically useful for sensitizing NPC to chemotherapy. Further studies on the therapeutic role of NGFR monoclonal antibody in modulating chemosensitivity are warranted for the development of NGFR as molecular target for NPC treatment.