A combination of methotrexate and irradiation promotes cell death in NK/T-cell lymphoma cells via down-regulation of NF-κB signaling.

Nasal NK/T-cell lymphoma (NKTL) is a highly aggressive disease. Although radiotherapy is the first-line of treatment for NKTL, the clinical outcome is poor. Thus, there is a need for an effective radiosensitizer to improve the survival rate of patients. NF-κB activation contributes to cell survival as well as chemo- and radio-resistance in various cancer cells. In NKTL, the constitutive activation of NF-κB is also a critical factor. In the present study, we used two EBV-expressing NKTL cell lines (Hank-1 and NK-92) to evaluate the radiosensitizing effect of methotrexate (MTX), highlighting the role of NF-κB. Combined treatment of MTX and IR significantly induced apoptosis and growth inhibition in both NKTL cells. The synergistic cytotoxicity was correlated with blocking nuclear NF-κB and suppressing expression of NF-κB-mediated anti-apoptotic proteins. These data suggest that the combined treatment with MTX and IR can inhibit IR-induced NF-κB activation in NKTL cells. Taken together, co-treatment with MTX and IR may provide a therapeutic advantage for patients with NKTL.