Inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents
Inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents
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DOI：
10.1016/j.leukres.2015.12.008
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发表时间：
2016-02-01
影响因子：
2.7
通讯作者：
Hara, Shuuji
中科院分区：
文献类型：
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作者：
Matsumoto, Taichi;Jimi, Shiro;Hara, Shuuji
尽管最近开发了抗骨髓瘤的药物，但高危多发性骨髓瘤的预后仍然很差。因此，需要新的有效的治疗策略来治疗这种疾病。据报道，高强度的18-氟代脱氧葡萄糖正电子发射断层扫描是骨髓瘤的高危因素，提示葡萄糖摄取可作为高危骨髓瘤的治疗靶点。在这项研究中，我们讨论了葡萄糖转运蛋白1(GLUT1)作为治疗葡萄糖摄取增加的骨髓瘤的靶点。我们发现骨髓瘤细胞系通过上调GLUT1的葡萄糖摄取活性而升高。选择性GLUT1抑制剂STF-31可完全抑制表达GLUT1的骨髓瘤细胞的葡萄糖摄取活性并诱导其凋亡。另一方面，该制剂对正常外周血单核细胞几乎没有显示出细胞毒性。此外，STF-31还协同增强了马法兰、阿霉素和硼替佐米诱导的细胞死亡。Glut1可能是治疗葡萄糖摄取升高的骨髓瘤的有效靶点。(C)2015爱思唯尔有限公司。保留所有权利。
Despite the recent development of anti-myeloma drugs, the prognosis of high-risk multiple myeloma remains poor. Therefore, new effective treatment strategies for this disease are needed. It has been reported that high intensity of 18-fluorodeoxyglucose positron emission tomography is high-risk factor in myeloma, suggesting that glucose uptake can be therapeutic target in high-risk myeloma. In this study, we addressed the utility of glucose transporter 1 (GLUT1) as a therapeutic target for myeloma with increased glucose uptake. We found myeloma cell lines with elevated glucose uptake activity via GLUT1 up-regulation. STF-31, a selective GLUT1 inhibitor, completely suppressed the glucose uptake activity and induced apoptosis in GLUT1 expressing myeloma cells. On the other hand, this agent little shows the cytotoxicity in normal peripheral blood mononuclear cells. Moreover, STF-31 synergistically enhanced the cell death induced by melphalan, doxorubicin, and bortezomib. GLUT1 may be promising therapeutic target in myeloma with elevated glucose uptake. (C) 2015 Elsevier Ltd. All rights reserved.