南京医科大学学报（自然科学版）2018，Vol.38Issue(4)：470-475,6.DOI:10.7655/NYDXBNS20180409
IL-1β和TNF-α通过骨髓MSCs降低多西环素对骨髓瘤细胞株H929的细胞毒性作用
IL-1β and TNF-α reduce cytotoxic effects of doxycycline to myeloma cell line H929 via bone marrow derived mesenchymal stem cells
摘要
Abstract
Objective:Bone marrow derived mesenchymal stem cells(MSCs)in bone marrow microenvironment was found to be involved in the chemoresistance of myeloma cells. In this study, we investigate the role of IL-1β or TNF-α-treated bone marrow MSCs in chemosensitivity of myeloma cell line H929 to doxycycline(DOX)in vitro, and find some possible mechanisms. Methods:CCK8 assay was employed to measure the proliferative rate of H929 cells in the presence of DOX at different concentration, either alone or coculture with bone marrow MSCs pretreated with IL-1β or TNF-α or not. The apoptotic ratio of H929 cells treated with DOX in the presence of IL-1β or TNF-α-treated bone marrow MSCs or not was determine by flow cytometry(FCM). FCM was also used with real time fluorescence quantitative polymerase chain reaction(RT-qPCR)to measure vascular cell adhesion molecule type one(VCAM-1) on MSCs. The p-Erk1/2 expression level in H929 was measured by Western blot. Results:DOX inhibited the proliferation and induced apoptosis of H929 in a time and dose-dependent manner. IL-1β or TNF-α-pretreated bone marrow MSCs reduced the cytotoxic effects of DOX in H929 cells. Expression level of p-Erk1/2 was down-regulated in H929 cells in the presence of DOX treatment, and this down-regulating effect of DOX was most pronounced when H929 cells were co-cultured with IL-1β or TNF-α-pretreated bone marrow MSCs. In addition, we found that VCAM-1 expression of bone marrow MSCs was up-regulated by IL-1β or TNF-α treatment. Conclusion: DOX was shown to have cytotoxicity to myeloma cells line H929 in a time and dose-dependent manner in vitro. IL-1β or TNF-α could abrogate the cytotoxic effects of DOX in H929 cells indirectly via bone marrow MSCs. Erk pathway in H929 cells and VCAM-1 expression on MSCs may be involved in this myeloma-protective effects by IL-1β or TNF-α.关键词
多发性骨髓瘤/多西环素/骨髓间充质干细胞/IL-1β/TNF-α/p-Erk1/2Key words
multiple myeloma/doxycycline/mesenchymal stem cells/IL-1β/TNF-α/p-Erk1/2分类
医药卫生引用本文复制引用
陆萍,费小明,汤郁,叶炜,颜玲玲,朱彦..IL-1β和TNF-α通过骨髓MSCs降低多西环素对骨髓瘤细胞株H929的细胞毒性作用[J].南京医科大学学报（自然科学版）,2018,38(4):470-475,6.基金项目
国家自然科学基金(81202358,81571582) （81202358,81571582）
江苏省卫生计生科研项目(Z201512) （Z201512）
