Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo.

Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo.
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DOI:
10.1111/cas.12436
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发表时间:
2014-07
期刊:
影响因子:
5.7
通讯作者:
Xu H
Xu H
中科院分区:
医学2区
文献类型:
--
作者:
Mei Q;Li F;Quan H;Liu Y;Xu H

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骨肉瘤通常发生在间充质来源的组织中,并且是最恶性的骨肿瘤,其特征在于高局部侵袭性,具有较差的治疗结果。白消安已被广泛用于治疗CML。白消安对骨肉瘤的治疗作用至今未见报道。在这里,我们发现白消安剂量依赖性地降低细胞活力和增殖,并诱导细胞凋亡,衰老和活性氧水平在两个骨肉瘤细胞系。此外,一系列功能丧失和功能获得实验进一步表明白消安可能通过上调microRNA-200(miR-200)家族,随后下调其靶基因ZEB 1和ZEB 2而具有抗骨肉瘤作用。此外,白消安治疗可能抑制裸鼠移植骨肉瘤的生长。综上所述,我们的数据表明白消安可能通过激活miR-200家族下调ZEB 1和ZEB 2而具有抗骨肉瘤作用,突出了使用白消安作为骨肉瘤新疗法的可能性。
Osteosarcoma typically arises in tissues of mesenchymal origin, and is the most malignant bone tumor characterized by high local aggressiveness, with poor therapeutic outcome. Busulfan has been widely used to treat CML. So far, there are no reports on the therapeutic effect of busulfan on osteosarcoma. Here, we showed that busulfan dose-dependently reduced the cell viability and proliferation, and induced cell apoptosis, senescence, and reactive oxygen species levels in two osteosarcoma cell lines. Moreover, a series of loss-of-function and gain-of-function experiments further indicated that busulfan may have its anti-osteosarcoma effect by upregulating the microRNA-200 (miR-200) family which subsequently downregulated its target genes ZEB1 and ZEB2. Furthermore, treatment with busulfan potentially inhibited the growth of implanted osteosarcoma in nude mice. Taken together, our data suggest that busulfan may have an anti-osteosarcoma effect through downregulating ZEB1 and ZEB2 through activating the miR-200 family, highlighting a possibility of using busulfan as a novel therapy for osteosarcoma.
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