論文 - 詳細
| RRC ID | 77166 |
|---|---|
| 著者 | Matsumoto T, Jimi S, Hara S, Takamatsu Y, Suzumiya J, Tamura K. |
| タイトル | Importance of inducible multidrug resistance 1 expression in HL-60 cells resistant to gemtuzumab ozogamicin. |
| ジャーナル | Leuk Lymphoma |
| Abstract |
Resistance to gemtuzumab ozogamicin (GO) hampers the effective treatment of refractory acute myeloid leukemia (AML). To clarify the mechanism of resistance to GO, HL-60 cells were persistently exposed to GO in order to establish GO-resistant HL-60 (HL-60/GOR) cells. Multidrug resistance 1 (MDR-1) was strongly expressed in HL-60/GOR cells, but not in HL-60 cells. Although withdrawal of GO after the chronic exposure of HL-60/GOR cells to this compound gradually decreased MDR-1 expression to trace levels, reintroducing GO restored high MDR-1 expression in HL-60/GOR cells, but not in HL-60 cells. These results indicate that HL-60/GOR cells acquired the ability to induce MDR-1 expression in response to GO. U0126, a MEK1/2 inhibitor, prevented GO-inducible MDR-1 expression and abrogated GO resistance in HL-60/GOR cells. These results suggest that in the clinical use of GO, inducible MDR-1 expression in tumor cells should be investigated before treatment with GO. If the cells are positive then MEK1/2 inhibitors may be effective in overcoming resistance to GO. |
| 巻・号 | 53(7) |
| ページ | 1399-405 |
| 公開日 | 2012-7-1 |
| DOI | 10.3109/10428194.2012.656102 |
| PMID | 22242821 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* Aminoglycosides / pharmacology* Antibodies, Monoclonal, Humanized / pharmacology* Antineoplastic Agents / pharmacology Blotting, Western Butadienes / pharmacology Cell Survival / drug effects Cell Survival / genetics Dose-Response Relationship, Drug Drug Resistance, Neoplasm / drug effects Drug Resistance, Neoplasm / genetics* Flow Cytometry Gemtuzumab Gene Expression Regulation, Leukemic / drug effects* HL-60 Cells Humans Leukemia, Promyelocytic, Acute / genetics Leukemia, Promyelocytic, Acute / metabolism Leukemia, Promyelocytic, Acute / pathology MAP Kinase Kinase 1 / antagonists & inhibitors MAP Kinase Kinase 1 / metabolism MAP Kinase Kinase 2 / antagonists & inhibitors MAP Kinase Kinase 2 / metabolism Nitriles / pharmacology Reverse Transcriptase Polymerase Chain Reaction |
| IF | 2.969 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | HL60(RCB0041) |