Open AccessBusulfan inhibits growth of human osteosarcoma through miR‐200 family micro RNA s in vitro and in vivo
Author(s) -
Mei Qiang,
Li Fang,
Quan Hongyu,
Liu Yunlai,
Xu Haidong
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12436
Subject(s) - osteosarcoma , busulfan , cancer research , cell growth , mesenchymal stem cell , apoptosis , in vivo , biology , chemistry , stem cell , microbiology and biotechnology , biochemistry , genetics , hematopoietic stem cell transplantation
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.