Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib
Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib
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DOI：
10.1007/s12032-016-0767-3
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发表时间：
2016-05-01
期刊：
影响因子：
3.4
通讯作者：
Luwor, Rodney B.
中科院分区：
文献类型：
--
作者：
Areeb, Zammam;Stylli, Stanley S.;Luwor, Rodney B.
多形性胶质母细胞瘤是中枢神经系统最具侵袭性和致命性的肿瘤，治疗策略有限，因此寻找有效的新型治疗药物至关重要。为了检验蛋白酶体抑制剂的有效性，我们测试了波特佐米、卡菲佐米、甲磺酸那法莫斯特、甲磺酸加贝酯和乙酰水杨酸对胶质母细胞瘤细胞存活、迁移和侵袭的影响。硼替佐米和卡菲佐米均能显著降低细胞存活率，而甲磺酸那法莫他酯、甲磺酸加贝酯和乙酰水杨酸则无此作用。随后的测试显示，在NM浓度下，卡菲佐米显著降低了细胞存活率。卡菲佐米还减少了所有四种胶质母细胞瘤细胞的细胞迁移、MMP2的分泌和激活以及细胞侵袭。综上所述，卡菲佐米是FDA批准的治疗多形性胶质母细胞瘤的一种新型药物。
Glioblastoma multiforme is the most aggressive and lethal tumor of the central nervous system with limited treatment strategies on offer, and as such the identification of effective novel therapeutic agents is paramount. To examine the efficacy of proteasome inhibitors, we tested bortezomib, carfilzomib, nafamostat mesylate, gabexate mesylate and acetylsalicylic acid on glioblastoma cell viability, migration and invasion. Both bortezomib and carfilzomib produced significant reduction of cell viability, while nafamostat mesylate, gabexate mesylate and acetylsalicylic acid did not. Subsequent testing showed that carfilzomib significantly reduced cell viability at nM concentrations. Carfilzomib also reduced cell migration, secretion and activation of MMP2 and also cell invasion of all four glioblastoma cells tested. In summary, carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme.