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
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- 作者：Masanobu Tsubaki ; Makiko Komai ; Tatsuki Itoh ; Motohiro Imano ; Kotaro Sakamoto ; Hirotaka Shimaoka ; Tomoya Takeda ; Naoki Ogawa ; Kenji Mashimo ; Daiichiro Fujiwara ; Junji Mukai ; Katsuhiko Sakaguchi ; Takao Satou ; Shozo Nishida
- 关键词：MM ; multiple myeloma ; MDR ; multi-drug resistance ; MDR1 ; multidrug resistance protein 1 ; ATP ; adenosine triphosphate ; PBS ; phosphate buffer saline.
- 刊名：Leukemia Research
- 出版年：January, 2014
- 年：2014
- 卷：38
- 期：1
- 页码：121-130
- 全文大小：2249 K
文摘
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.