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

Abstract

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 G2/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.

Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells

“…Previous studies have already proven the inhibitory effects of betulinic acid on clonogenic survival in human lung cancer, breast cancer and glioma cells, especially under hypoxic conditions [22,23,42]. Moreover, an inhibitory effect on clonogenic survival was also shown for different tumor cells with reduced CA 9 expression or CA IX activity [6,22,43,44]. Therefore, the combination of the betulin scaffold and the CA IX-inhibiting sulfonamide group (in 13b and 15b) reinforces the inhibitory effect on clonogenic survival compared to the precursors 13 and 15 in breast cancer cell lines.…”

Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

“…Radiation sensitivity increased in hypoxic CNE-2 cells following CAIX inhibition. These findings point to CAIX as a potential therapeutic target for radioresistant human nasopharyngeal carcinoma 80 (p2) .…”

Complete response with combined therapy in a patient with brain metastasis from nasopharyngeal carcinoma: case report and literature review

“… 2 Radiotherapy is the most powerful treatment modality for NPC. 3 Unfortunately, approximately 15% to 30% of patients with NPC develop metastasis after initial treatment. 4 The common metastatic sites of NPC are bone, lung, and liver.…”