In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A.
Epstein-Barr virus (EBV)-associated nasal T/natural killer (NK) cell lymphoma has often been reported in Asian countries and has been recently confirmed as a novel clinicopathological entity. The prognosis of advanced stage disease is quite poor and an effective chemotherapeutic modality is strongly advocated. We have established the novel cell line NK-YS, which preserves the original characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using this cell line, we investigated the induction of apoptosis by apoptosis-inducing agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp but not p53. To overcome this drug resistance, we added cyclosporine A (CsA) and these agents to culture media as a P-gp antagonist. The combination of CsA and etoposide or CsA and doxorubicin induced apoptotic cell death. These results indicated that P-gp-mediated drug resistance is an essential mechanism of drug resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer agents with CsA may have an important place in the establishment of a curative therapy for disseminated nasal angiocentric NK cell lymphoma.
Uno
M
M
Second Department of Internal Medicine, Okayama University Medical School, Okayama, Japan. firefly@oka.urban.ne.jp
Tsuchiyama
J
J
Moriwaki
A
A
Noguchi
T
T
Mizoguchi
K
K
Ogino
T
T
Yoshino
T
T
Okada
S
S
Harada
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007694:Killer Cells, Natural; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000821:virology; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; D019384:Nucleic Acid Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D016572:Cyclosporine