Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, 110# Xiangya Road, Changsha, 410011, China.
Xiangya Medical School, Central South University, Changsha, 410011, China.
Cancer Lett. 2021 Nov 1;520:307-320. doi: 10.1016/j.canlet.2021.08.009. Epub 2021 Aug 12.
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）是一种无法治愈的疾病，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 MM 细胞中的一个稀有群体，被认为是导致 MM 患者耐药和高复发率的主要原因。因此，开发新的策略来消除 MMSCs 可能有利于骨髓瘤的治疗。在这项研究中，基于药物重定位策略，我们发现阿苯达唑（ABZ），一种广谱抗寄生虫药物，在体外和体内选择性抑制多发性骨髓瘤细胞的增殖，并减少 MM 中醛脱氢酶（ALDH）阳性 MMSCs 的数量。此外，ABZ 处理后的 MM 细胞的 RNA-seq 显示，核因子 kappa-B（NF-κB）通路的抑制是 ABZ 对抗 MM 的关键介质。此外，我们证明 ABZ 可以通过减少 ALDH1 MMSCs 的数量来重新敏感对硼替佐米耐药的细胞并克服 MMSCs 诱导的硼替佐米耐药。我们的研究结果为利用先前已知的具有药理活性的药物阿苯达唑治疗多发性骨髓瘤提供了临床前证据。
