論文 - 詳細
RRC ID | 44739 |
---|---|
著者 | Tsubaki M, Komai M, Itoh T, Imano M, Sakamoto K, Shimaoka H, Takeda T, Ogawa N, Mashimo K, Fujiwara D, Mukai J, Sakaguchi K, Satou T, Nishida S. |
タイトル | By inhibiting Src, verapamil and dasatinib overcome multidrug resistance via increased expression of Bim and decreased expressions of MDR1 and survivin in human multidrug-resistant myeloma cells. |
ジャーナル | Leuk Res |
Abstract |
The calcium channel blocker verapamil inhibits the transport function of multidrug resistance protein 1 (MDR1). Although verapamil acts to reverse MDR in cancer cells, the underlying mechanism remains unclear. In the present study, we investigated the mechanism of reversing MDR by verapamil in anti-cancer drug-resistant multiple myeloma (MM) cell lines. We found that verapamil suppresses MDR1 and survivin expressions and increases Bim expression via suppression of Src activation. Furthermore, dasatinib reversed the drug-resistance of the drug-resistant cell lines. These findings suggest that Src inhibitors are potentially useful as an anti-MDR agent for the treatment of malignant tumor cells. |
巻・号 | 38(1) |
ページ | 121-30 |
公開日 | 2014-1-1 |
DOI | 10.1016/j.leukres.2013.10.017 |
PII | S0145-2126(13)00371-8 |
PMID | 24239173 |
MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Antineoplastic Agents / pharmacology Apoptosis Regulatory Proteins / metabolism* Bcl-2-Like Protein 11 Blotting, Western Cell Line Cell Line, Tumor Cell Survival / drug effects Dasatinib Dexamethasone / pharmacology Down-Regulation / drug effects Doxorubicin / pharmacology Drug Resistance, Multiple / drug effects Drug Resistance, Neoplasm / drug effects Drug Synergism Enzyme Activation / drug effects Humans Inhibitor of Apoptosis Proteins / metabolism* Melphalan / pharmacology Membrane Proteins / metabolism* Multiple Myeloma / metabolism Multiple Myeloma / pathology Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins / metabolism* Pyrimidines / pharmacology* Survivin Thiazoles / pharmacology* Up-Regulation / drug effects Verapamil / pharmacology* src-Family Kinases / metabolism* |
IF | 2.214 |
引用数 | 33 |
WOS 分野 | ONCOLOGY HEMATOLOGY |
リソース情報 | |
ヒト・動物細胞 | ST2(RCB0224) |