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 evaluate the therapeutic effect of busulfan on an osteosarcoma in vivo, we generated a mouse model by orthotopically injecting luciferase-transfected U2OS (U2OS-LUC) into the tibia of nude mice, as it is one of the most common locations of primary osteosarcoma in humans. Tumor growth was monitored by bioluminescence imaging (Fig. 5a). The bioluminescence levels in the mice without busulfan treatment increased by 3.8 ± 0.5% fold, whereas the bioluminescence levels in the mice that received busulfan treatment decreased by 74.3 ± 11.6%, in 1 month (Fig. 5b,c), suggesting that the tumor growth was significantly inhibited in the mice that received busulfan. The TUNEL assay further confirmed that busulfan induced significant apoptosis of osteosarcoma cells in vivo (Fig. 5d). Taken together, busulfan inhibited osteosarcoma growth in vivo.
Affiliation: 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China.