Magnetic Nanoparticles of Fe3O4 Enhance Artesunate-inducing Apoptosis of SKM-1 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of the copolymer of magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)) and artesunate (ART) on myelodysplastic syndromes (MDS) cell line SKM-1 cells and the potential mechanisms.</p><p><b>METHODS</b>The protein expression levels of BCL-2, BAX, Caspase-3, and Survivin in SKM-1 cells treated with or without the co-polymer were measured by Western blot. The co-polymer-induced apoptosis rate of SKM-1 cells was measured by flow cytometry.</p><p><b>RESULTS</b>The apoptosis rate of SKM-1 cells in the copolymer groups was higher than that in both MNPs-Fe(3)O(4) and artesunate groups alone. The MNPs-Fe(3)O(4) may enhance ART-induced cell apoptosis. Western blot assay showed that the expression of survivin and BCL-2 protein were down-regulated in the ART group, and this down-regulation was even more significant in the group of copolymer of ART with MNPs-Fe(3)O(4). The levels of BAX were increased both in ART group and the copolymer of ART with MNPs-Fe(3)O(4) group, as compared with control group and MNPs-Fe(3)O(4) group. The levels of active-caspase-3 were obviously up-regulated when the ART was combined with the MNPs-Fe(3)O(4). The copolymer of ART with MNPs-Fe(3)O(4) could trigger changes in the expression levels of apoptosis-related genes in SKM-1 cells, among which up-regulation of BAX and down-regulation of survivin and BCL-2 are the 2 major alterations.</p><p><b>CONCLUSION</b>Artesunate can induce the apoptosis of SKM-1 cells, and MNPs-Fe(3)O(4) may enhance the cell apoptosis induced by ART.</p>

BMMSC from blastic phase CML down-regulate leukemia cell apoptosis / 中国实验血液学杂志

The purpose of this study was to investigate the effect of bone marrow mesenchymal stem cells (BMMSC) from patients with chronic myeloid leukemia (CML) in blastic phase (Bp) on K562 cells and the primary CML-Bp cells, and to explore its potential mechanisms. K562 cells and primary CML-Bp cells were co-cultured with BMMSC of different groups; the cell proliferation was detected by MTT method, the cell apoptosis rate and mitochondrial membrane potential were measured by flow cytometry, the expression levels of Caspase-8, Caspase-9, and activated Caspase-3 in cells were measured by Western blot. The results showed that the CML-Bp BMMSC could enhance the survival rate of K562 cells treated with adviamycin (ADM) and display protective effect on K562 cells and primary CML-Bp mononuctear cells, inhibited ADM-induced leukimia cell apoptosis (P < 0.05); as compared with CML-chronic phase (CML-Cp) BMMSC and normal BMMSC, the CML-Bp BMMSC showed the highest protective effect on leukemic cells, the mitochondrial membrane potential of co-cultured cells slightly droped (P < 0.05). In the CML-Bp BMMSC cultured with K562 cells, the expression level of caspase-3 was more down-regulated than that in K562 alone plus ADM group, while the expression of caspase-9 significantly increased (P < 0.05). It is concluded that the CML-Bp BMMSC down-regulates ADM-induced leukemia cell appoptosis, its mechanism may relate with the inhibition of mitochondrial membrane potential drop, the stabilization of unactive expression of caspase-9 and down-regulation of caspase-3 expression.

Inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia cells and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia (CML) cells and its possible mechanism.</p><p><b>METHODS</b>The effects of rapamycin at various concentrations on cell proliferation of CML cell line K562 cells were analyzed by MTT. The expressions of mTOR, 4E-BP1 and p70S6K at protein and mRNA level in K562 cells with rapamycin treatment were detected by Western blot and RT-PCR. The protein expressions and phosphorylation of mTOR, 4E-BP1 and p70S6K in primary bone marrow cells from CML patients at chronic phase (CP) were also investigated by Western blot, bone marrow cells from healthy people were used as control. Data were analyzed by the χ(2) test, Fisher's exact test and one-way analysis of variance (ANOVA).</p><p><b>RESULTS</b>The phosphorylation of mTOR, 4E-BP1 and p70S6K were significantly increased in CML bone marrow cells compared with that of normal control (70.6% vs 30.0%, 76.5% vs 40.0%, 73.5% vs 20.0%, respectively, P < 0.05). The proliferation of K562 cells was significantly inhibited with 20 nmol/L and more rapamycin treatment. The phosphorylation of mTOR was decreased after rapamycin treatment, as well as the expressions of 4E-BP1 and p70S6K at protein and mRNA level (P < 0.05).</p><p><b>CONCLUSION</b>mTOR signaling played an important role in CML pathogenesis, and rapamycin could decrease CML cells proliferation by inhibiting the activity of mTOR signaling in vitro.</p>