| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041) |
