Jin Weimei, Wang Xiaoli, Zeng Yuxiao, Lan Yifen, Wang Xiaoqiu
Hematology Department, Lishui People's Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui College, Lishui, Zhejiang, China.
Neoplasma. 2021 Mar;68(2):404-415. doi: 10.4149/neo_2020_200923N1010. Epub 2021 Jan 14.
Multiple myeloma (MM) is incurable cancer in the blood system. Magnolol is an effective component against various cancers. This study tried to investigate the effect and mechanism of magnolol on MM via regulating miR-129. Human normal plasma cells (nPCs) and MM cells U266 and LP1 were used in this study, accompanied by treatment of magnolol. The miR-129 inhibitor was transfected into U266 and LP1 cells during experiments. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were tested by wound healing assay and Transwell assay. And Annexin-V-FITC/PI assay was utilized to assess cell apoptosis. miR-129, miR-1271-5p, miR-342-3p, and miR-124-3p expressions were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blot was adopted to evaluate Cyclin D1, matrix metalloprotein (MMP)-7, MMP-9, phosphorylation (p)-IκBα, p-p65, and p65 protein levels. In U266 and LP1 cells, with magnolol concentration increasing, cell viability, migration, and invasion rates, Cyclin D1, MMP-7, and MMP-9 expressions decreased, while cell apoptosis rose. And magnolol increased the miR-129 expression in MM cells. Besides, miR-129 inhibitor antagonized the above-mentioned effect of magnolol and partly offset the magnolol-induced decrease of p-IκBα and p-p65 expression, as well as the ratio of p-p65 to p65 in U266 and LP1 cells. Magnolol suppressed cell migration and invasion and induced cell apoptosis via inhibiting NF-κB pathway activation, by upregulating miR-129 in MM.
多发性骨髓瘤（MM）是一种血液系统中的不治之症。厚朴酚是一种对多种癌症有效的成分。本研究试图通过调节miR-129来探究厚朴酚对MM的作用及机制。本研究使用了人正常浆细胞（nPCs）以及MM细胞U266和LP1，并进行了厚朴酚处理。实验过程中，将miR-129抑制剂转染到U266和LP1细胞中。采用细胞计数试剂盒-8法检测细胞活力。通过伤口愈合实验和Transwell实验检测细胞迁移和侵袭能力。并利用膜联蛋白-V-异硫氰酸荧光素/碘化丙啶法评估细胞凋亡。通过定量逆转录-聚合酶链反应（qRT-PCR）检测miR-129、miR-1271-5p、miR-342-3p和miR-124-3p的表达，并采用蛋白质免疫印迹法评估细胞周期蛋白D1、基质金属蛋白酶（MMP）-7、MMP-9、磷酸化（p）-IκBα、p-p65和p65的蛋白水平。在U266和LP1细胞中，随着厚朴酚浓度的增加，细胞活力、迁移和侵袭率、细胞周期蛋白D1、MMP-7和MMP-9的表达均降低，而细胞凋亡增加。并且厚朴酚增加了MM细胞中miR-129的表达。此外，miR-129抑制剂拮抗了厚朴酚的上述作用，并部分抵消了厚朴酚诱导的U266和LP1细胞中p-IκBα和p-p65表达的降低，以及p-p65与p65的比值。厚朴酚通过上调MM中的miR-129，抑制NF-κB通路激活，从而抑制细胞迁移和侵袭并诱导细胞凋亡。
