Albendazole inhibits NF-κB signaling pathway to overcome tumor stemness and bortezomib resistance in multiple myeloma
| Autor: | Zhenzhen Li, Jing Liu, Yibin Zhang, Lingli Yuan, Ji Zhang, Ling Xiao, Haiqin Wang, Fanjie Gong, Yanpeng Wang, Hui Zhou, Xiaojuan Xiao, Lei Hu, Hui Yi, Long Liang, Chong-Wen Dai, Mao Ye, Hongling Peng, Saiqun Luo, Ruijuan Li, Xiaokai Shen |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Population Aldehyde dehydrogenase Apoptosis Drug resistance Albendazole Aldehyde Dehydrogenase 1 Family Bortezomib In vivo Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Humans RNA-Seq education Multiple myeloma education.field_of_study biology business.industry NF-kappa B medicine.disease In vitro Drug repositioning Oncology Drug Resistance Neoplasm biology.protein Cancer research Neoplastic Stem Cells business Multiple Myeloma medicine.drug Signal Transduction |
| Zdroj: | Cancer letters. 520 |
| ISSN: | 1872-7980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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