Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1⁺ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.

多发性骨髓瘤 (MM) 是无法治愈的，是浆细胞中第二常见的血液系统恶性肿瘤。多发性骨髓瘤干细胞样细胞 (MMSCs) 是一种罕见的 MM 细胞群，被认为是 MM 患者耐药和高复发率的主要原因。因此，开发根除 MMSCs 的新策略可能有利于骨髓瘤的治疗。在本研究中，基于药物重新定位策略，我们发现广谱抗寄生虫药物阿苯达唑（ABZ）在体外和体内选择性地抑制多发性骨髓瘤细胞的增殖并减少醛脱氢酶（ALDH）阳性的数量。 MM中的MMSC。此外，ABZ 处理后 MM 细胞的 RNA-seq 显示，抑制核因子 kappa-B (NF-κB) 途径是 ABZ 对抗 MM 的关键介质。而且，⁺ MMSCs 号码。我们的研究结果为利用先前已知的药理活性药物阿苯达唑治疗多发性骨髓瘤提供了临床前证据。