浙江医学2025，Vol.47Issue(17)：1824-1829,6.DOI:10.12056/j.issn.1006-2785.2025.47.17.2024-2240
甲苯咪唑抗多发性骨髓瘤细胞效应与作用机制研究
Study on the anti-multiple myeloma cell effect of mebendazole and its mechanism
摘要
Abstract
Objective To observe the effect of mebendazole(MBZ)on multiple myeloma(MM)cells,and explore its mechanism.Methods MM cell lines(H929,U266,and LP1 cells)intervened with different concentrations of MBZ were observed.The cell proliferation rate was detected by the cell counting kit-8(CCK-8)method,the apoptosis rate was detected by flow cytometry,and the morphological changes of the cells were observed under a microscope.Western blotting was used to detect the expression of apoptotic proteins,autophagy-related proteins,mammalian target of rapamycin(mTOR)/serine/threonine protein kinase(AKT)pathway and epigenetically regulated proteins.Results MBZ had a dose-dependent growth inhibitory effect on MM cell lines,and the sensitivity of different cell lines to MBZ varied.Morphological observation revealed that MM cells exhibited typical apoptotic morphology under the action of MBZ.MBZ induced apoptosis in H929 and U266 cells,and the apoptosis rate increased with the rising concentration of MBZ.With the increase of MBZ concentration,the expressions of apoptosis-related protein cleaved poly-adenosine diphosphate ribose polymerase 1(PARP1)and cleaved caspase3(cleaved-caspase3)in H929 and U266 cells were up-regulated,while the protein expressions of phosphorylated mTOR(p-mTOR),mTOR,phosphorylated AKT(p-AKT),and AKT were down-regulated.The expressions of epigenetics-related proteins Jumonji domain protein 2A(JMJD2A),silencing information regulator 1(SIRT1),and the trimethylation modification of lysine 27 at histone H3(H3K27Me3)were downregulated.With the prolonged intervention time of MBZ,the expressions of autophagy-related protein sequestosome1/p62 and the isoforms of microtubule-associated protein light chain 3(LC3)LC3a and LC3b were all downregulated.Conclusion MBZ can effectively inhibit the proliferation of MM cells and induce cell apoptosis.Its mechanism may involve decreasing the expression of proteins such as p-mTOR,mTOR,p-AKT,AKT,JMJD2A,SIRT1,and H3K27Me3,and being associated with the autophagy pathway.关键词
甲苯咪唑/多发性骨髓瘤/细胞凋亡/自噬Key words
Mebendazole/Multiple myeloma/Cell apoptosis/Autophagy引用本文复制引用
郑文韬,范京圳,黄河..甲苯咪唑抗多发性骨髓瘤细胞效应与作用机制研究[J].浙江医学,2025,47(17):1824-1829,6.基金项目
温州市科学技术局基础性公益科研项目(Y2023405) （Y2023405）
