RNAi-mediated knockdown of CAIX enhances the radiosensitivity of nasopharyngeal carcinoma cell line, CNE-2

Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX. Results showed that Lipofectamine 2000 effectively delivered siRNA into the CNE-2 cells, which resulted in the decrease of CAIX expression and cell viability, decrease in cell proliferation and colony formation, and increase in the number of CNE-2 cells stuck in the G(2)/M phase of the cell cycle upon induction of ionizing radiation. Increased sensitivity of radiotherapy in CNE-2 cells under hypoxic conditions was correlated with the suppression of CAIX. Cells treated with irradiation in addition to CAIX-siRNA1 demonstrated reduced radiobiological parameters (survival fraction at 2 Gy [SF2]) compared with those treated with irradiation only, with a sensitization-enhancing ratio of 1.47. These findings suggest that CAIX can be a promising therapeutic target for the treatment of radioresistant human NPC.