論文 - 詳細
RRC ID | 57753 |
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著者 | Hayano A, Takashima Y, Yamanaka R. |
タイトル | Cell-type-specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells. |
ジャーナル | Int J Clin Oncol |
Abstract |
BACKGROUND:Methotrexate (MTX) is used in first-line treatment of primary central nervous system lymphoma (PCNSL), but most cases result in relapse-acquired resistance to MTX. However, only few studies have reported on internal changes and chemotherapies in PCNSL. METHODS:In this study, we generated two MTX-resistant PCNSL cell lines, designated MTX-HKBML and MTX-TK, in addition to a MTX-resistant Burkitt lymphoma cell line, designated MTX-RAJI. We examined gene expression changes and drug sensitivity to a proteasome inhibitor, bortezomib, in these cells. RESULTS:Cytotoxic tests revealed that the 50% inhibitory concentration for MTX in MTX-HKBML is markedly higher than that in the other two cell lines. Expression of the genes in MTX and folate metabolisms, including gamma-glutamyl hydrolase and dihydrofolate reductase, are upregulated in both MTX-HKBML and MTX-TK, whereas the gene expression of folylpolyglutamate synthetase, thymidylate synthase, and methylenetetrahydrofolate dehydrogenase 1 were upregulated and downregulated in MTX-HKBML and MTX-TK, respectively, on the other hand, bortezomib sensitivity was observed in MTX-TK, as compared with control TK, but not in MTX-HKBML. CONCLUSION:These results indicate the cell-type-specific changes downstream of metabolic pathways for MTX and folate, bortezomib sensitivity, and purine and pyrimidine syntheses, in each PCNSL cell line. The MTX-resistant lymphoma cell lines established may be useful for in vitro relapse models for MTX and development of salvage chemotherapy and drug discovery. |
巻・号 | 24(9) |
ページ | 1020-1029 |
公開日 | 2019-9-1 |
DOI | 10.1007/s10147-019-01451-9 |
PII | 10.1007/s10147-019-01451-9 |
PMID | 30993483 |
MeSH | Antineoplastic Combined Chemotherapy Protocols / pharmacology Bortezomib / administration & dosage Bortezomib / pharmacology* Cell Line, Tumor Central Nervous System Neoplasms / drug therapy* Central Nervous System Neoplasms / genetics Central Nervous System Neoplasms / pathology Drug Resistance, Neoplasm / drug effects* Folic Acid / genetics Folic Acid / metabolism Gene Expression Regulation, Neoplastic / drug effects Humans Lymphoma / drug therapy* Lymphoma / genetics Lymphoma / pathology Lymphoma, Non-Hodgkin / drug therapy Lymphoma, Non-Hodgkin / pathology Methotrexate / administration & dosage Methotrexate / pharmacology* Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics Minor Histocompatibility Antigens / genetics Molecular Targeted Therapy Peptide Synthases / genetics Thymidylate Synthase / genetics |
IF | 2.879 |
引用数 | 2 |
リソース情報 | |
ヒト・動物細胞 | HKBML(RCB0820) RAJI(RCB1647) |