Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo.
Bottom Line: 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.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.
Affiliation: 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China.Show MeSH
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Mentions: In order to find out whether upregulating the miRNA-200 family, or inhibiting ZEB1 and ZEB2, may produce the anti-osteosarcoma effect without the need of busulfan, we overexpressed miR-200a, miR-200b, miR-200c, miR-141, and miR-429, or inhibited ZEB1 and ZEB2, alone (without treatment of busulfan) in osteosarcoma cells. The anti-osteosarcoma effects of busulfan were partially mimicked by these approaches (Fig. 4). These gain-of-function experiments thus strengthened our findings and further showed that busulfan may produce its anti-osteosarcoma effect by upregulating ZEB1 and ZEB2 through activating the miRNA-200 family.
Affiliation: 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China.