Objective To study the effect of acute lymphoblastic leukemia (ALL) children bone marrow mesenchymal stem cells (MSCs) on the resistance of K562cell atd mechanism in vitro.Method MSCs were obtained from AL children bone marrow after derivation, cultivation and identification.The coculture of MSCs and K562 and K562 suspension were established.Effects of MSCs on the growth of K562 cells were investigated in vivo.The two kinds of cells treated with different concentration of adriamycin (ADM) and the rate of apoptosis was evaluated by flow cytometry.Cell cycle was determined by flow cytometry.RT-PCR was used to detect Bcl-2 and Bax in K562 cells.Result Compared with the cell growth curve of K562 alone, the K562 cell co-cultured with MSCs grew slower and the exponential phase of growth was not obvious.The apoptosis index of the K562 cells co- clutured with MSCs was (9.19 ±0.53)% examined by flow cytometry, and that of the K562 cells alone was 4.00 ± 0.37% respectively( P ＜ 0.05 ).The percentage of cells at G0/G1 phase was (50.2 ± 2.26) % and that at S phase was (37.03 ± 3.50) % in the group of K562 alone, but those of the K562 cells co - cultured with MSCs were (80.95 ± 3.83) % and ( 17.40 ± 1.50)% respectively( P ＜0.05).The result of RT-PCR suggested expression of Bcl-2/Bax of the K562 cell co-cultured with MSCs was higher than K562 alone.Conclusion ALL children MSCs suppressed the growth of K562 cell in vitro.Adhesion made K562 depress sensitive to ADM.The mechanism was perhaps caused by adhesion with MSCs, K562 cell cycle was changed and related to Bcl-2 gene high level expression.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.