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

作者：Kim Areumnuri; Lee Jung Eun; Jang Won Suk; Lee Sun Joo; Park Sunhoo; Kang Hye Jin; Lee Seung Sook

来源：Leukemia Research, 2012, 36(3): 350-357.

DOI：10.1016/j.leukres.2011.07.027

• Lymphoma
• Extranodal NK/T-cell
• Methotrexate
• Radiotherapy
• NF-kappa B

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-kappa B activation contributes to cell survival as well as chemo-and radio-resistance in various cancer cells. In NKTL, the constitutive activation of NF-kappa B 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-kappa B. 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-kappa B and suppressing expression of NF-kappa B-mediated anti-apoptotic proteins. These data suggest that the combined treatment with MTX and IR can inhibit IR-induced NF-kappa B activation in NKTL cells. Taken together, co-treatment with MTX and IR may provide a therapeutic advantage for patients with NKTL.

• 出版日期2012-3