Busulfan inhibits growth of human osteosarcoma through miR‐200 family micro RNA s in vitro and in vivo

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 osteosarc...

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Bibliographic Details
Published in:Cancer science 2014-07, Vol.105 (7), p.755-762
Main Authors: Mei, Qiang, Li, Fang, Quan, Hongyu, Liu, Yunlai, Xu, Haidong
Format: Article
Language:English
Subjects:
Apoptosis
Bone cancer
Bone tumors
Brain cancer
Busulfan
Cell growth
Cell viability
Enzymes
Experiments
Gene expression
Kinases
Laboratory animals
Mesenchyme
MicroRNAs
miRNA
Osteosarcoma
Reactive oxygen species
Senescence
Software
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Summary: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 micro RNA ‐200 (miR‐200) family which subsequently downregulated its target genes ZEB 1 and ZEB 2 . 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 ZEB 1 and ZEB 2 through activating the miR‐200 family, highlighting a possibility of using busulfan as a novel therapy for osteosarcoma.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12436