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热激蛋白(heat shock protein,HSP)作为分子伴侣,在蛋白质的折叠、装配、转运和降解、机体免疫、细胞凋亡等方面发挥重要作用。HSP在多发性骨髓瘤细胞中高表达,在骨髓瘤硼替佐米耐药的发生、发展中起极为重要的作用,并已成为多发性骨髓瘤治疗的一个新靶点。与骨髓瘤患者耐药相关的HSP主要包括HSP90、HSP70、HSP27。HSP90主要通过直接与其分子伴侣结合,扰乱客户蛋白(client protein)以及影响正常的凋亡途径发挥作用,临床上HSP90抑制剂正处于广泛研究中,并发现其可逆转骨髓瘤耐药。HSP70、HSP27亦与骨髓瘤耐药相关,但具体机制尚待进一步深入研究。本文主要介绍HSP家族在骨髓瘤硼替佐米耐药中的作用,对部分机制进行探讨,并对今后的研究重点进行展望。
Heat shock protein (HSP), as a chaperone, plays an important role in protein folding, assembly, transport and degradation, immunity and apoptosis. HSP is highly expressed in multiple myeloma cells and plays a very important role in the occurrence and development of myeloma bortezomib and has become a new target for the treatment of multiple myeloma. HSPs related to drug resistance in patients with myeloma mainly include HSP90, HSP70 and HSP27. HSP90 plays a role mainly through direct binding with its chaperone, disrupting client protein and affecting normal apoptosis pathway. Clinically, HSP90 inhibitors are under extensive research and found to reverse myeloma drug resistance. HSP70, HSP27 also associated with myeloma resistance, but the specific mechanism needs further study. This article mainly introduces the role of HSP family in myeloma Bortezomib resistance, discusses some mechanisms, and focuses on the future research prospects.