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Research Article

炖的果汁：蛋白质稳态机械抑制降低多发性骨髓瘤细胞系的细胞活力

卷 19, 期 2, 2019

页: [112 - 119] 页: 8

弟呕挨: 10.2174/1566524019666190305134441

价格: $65

摘要

简介：多发性骨髓瘤（MM）细胞在骨髓中积聚并产生大量免疫球蛋白，引起内质网应激和蛋白质处理机制的激活，如热休克蛋白反应，自噬和未折叠蛋白反应（UPR）。 方法：我们评估了用硼替佐米（B）与HSP70（VER-15508）和自噬（SBI-0206965）或UPR（STF-083010）抑制剂联合治疗后的细胞系活力。 结果：对于RPMI-8226，用B + VER + STF或B + VER + SBI处理72小时后，我们观察到15％的活细胞，但单独用B处理更好（90％的细胞死亡）。对于U266，用B + VER + STF或B + VER + SBI处理72小时导致20％的细胞活力，并且两种处理均优于单独使用B处理（40％的细胞死亡）。在两种三联体组合后，RPMI-8226和U266呈现XBP-1 UPR蛋白的过表达，表明它作为补偿机制起作用，试图使细胞处理否则致命的大量免疫球蛋白超载。 结论：我们的体外结果提供了额外的证据，可以探索蛋白质稳态抑制剂的组合作为MM的治疗选择。

关键词: 多发性骨髓瘤，蛋白酶体，HSP70，自噬，UPR，UPS。

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