title: A combination of methotrexate and irradiation promotes cell death in NK/T-cell lymphoma cells via down-regulation of NF-κB signaling.
abstract: 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.
authors: Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Science, Seoul, Republic of Korea.
authors: Areumnuri
authors: A
authors: Kim
authors: Jung-Eun
authors: JE
authors: Lee
authors: Won-Suk
authors: WS
authors: Jang
authors: Sun-Joo
authors: SJ
authors: Lee
authors: Sunhoo
authors: S
authors: Park
authors: Hye Jin
authors: HJ
authors: Kang
authors: Seung-Sook
authors: SS
authors: Lee
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D059248:Chemoradiotherapy; D003593:Cytoplasm / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D008727:Methotrexate / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D002588:Cesium Radioisotopes; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D008727:Methotrexate