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

Cancer Science

Qiang Mei¹  Fang Li¹  Hongyu Quan²  Yunlai Liu² 

[1] 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China;Department of Histology and Embryology, Third Military Medical University, Chongqing, China

关键词: Busulfan;    microRNAs;    osteosarcoma;    ZEB1;    ZEB2;   

DOI  :  10.1111/cas.12436

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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