Study on the Effect and Mechanism of Tetrandrine on Bone Marrow Mesenchymal Stem Cell-Mediated Drug Resistance in Leukemia
Objective:To explore the role of bone marrow mesenchymal stem cells(BMSC),an essential element of the bone marrow microenvironment,in multidrug resistance(MDR)of K562 cells,as well as the reversal effect of tetrandrine(TET)on BMSC-mediated MDR and its potential mechanism.Methods:A mixed co-culture system and a transwell co-culture system for BMSC and K562 cells were established,and the cells were divided into different groups and treated with daunorubicin(DNR)alone or combined with TET and DNR.The CCK-8 assay was used to detect the proliferation of K562 cells in each group,and the cell inhibition rate was calculated.Cytometric bead array(CBA)was used to detect the expression levels of IFN,IL-2,IL-6 and IL-10 in the supernatant of different groups.RT-qPCR and Western blot were used to detected the expression of STAT3 at mRNA and protein levels,respectively.Results:Compared with K562+DNR group,the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR group was significantly decreased(P＜0.05),while the levels of IL-6 in the culture supernatant and phosphorylated STAT3 in K562 cells were significantly increased(P＜0.05).Compared with K562+BMSC+DNR group,the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR+TET group was significantly increased(P＜0.05),while the level of IL-6 and phosphorylated STAT3 was significantly decreased(P＜0.05).Conclusion:BMSC can promote the drug resistance of leukemia cells,and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.
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NSTL
万方数据
维普
