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

Mei Q, Li F, Quan H, Liu Y, Xu H - Cancer Sci. (2014)

Bottom Line: Busulfan has been widely used to treat CML.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.

View Article: PubMed Central - PubMed

Affiliation: 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China.

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Busulfan inhibited osteosarcoma growth in vivo in a mouse model. (a) In order to evaluate the therapeutic effect of busulfan on osteosarcoma in vivo, we generated a mouse model by orthotopically injecting luciferase-transfected U2OS (U2OS-LUC) into the tibia of nude mice. One month later, busulfan was i.v. injected into the mice every other day for another month. (b,c) Tumor growth was monitored by bioluminescence imaging. We found a continuous growth of the implanted tumor in the control mice, but the tumor growth was significantly inhibited in the mice that received busulfan, shown by representative images (b), and by quantification (c). (d) TUNEL assay further confirmed that busulfan induced significant apoptosis of osteosarcoma cells in vivo. Scale bar = 40 μm.
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fig05: Busulfan inhibited osteosarcoma growth in vivo in a mouse model. (a) In order to evaluate the therapeutic effect of busulfan on osteosarcoma in vivo, we generated a mouse model by orthotopically injecting luciferase-transfected U2OS (U2OS-LUC) into the tibia of nude mice. One month later, busulfan was i.v. injected into the mice every other day for another month. (b,c) Tumor growth was monitored by bioluminescence imaging. We found a continuous growth of the implanted tumor in the control mice, but the tumor growth was significantly inhibited in the mice that received busulfan, shown by representative images (b), and by quantification (c). (d) TUNEL assay further confirmed that busulfan induced significant apoptosis of osteosarcoma cells in vivo. Scale bar = 40 μm.

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.


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

Mei Q, Li F, Quan H, Liu Y, Xu H - Cancer Sci. (2014)

Busulfan inhibited osteosarcoma growth in vivo in a mouse model. (a) In order to evaluate the therapeutic effect of busulfan on osteosarcoma in vivo, we generated a mouse model by orthotopically injecting luciferase-transfected U2OS (U2OS-LUC) into the tibia of nude mice. One month later, busulfan was i.v. injected into the mice every other day for another month. (b,c) Tumor growth was monitored by bioluminescence imaging. We found a continuous growth of the implanted tumor in the control mice, but the tumor growth was significantly inhibited in the mice that received busulfan, shown by representative images (b), and by quantification (c). (d) TUNEL assay further confirmed that busulfan induced significant apoptosis of osteosarcoma cells in vivo. Scale bar = 40 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317920&req=5

fig05: Busulfan inhibited osteosarcoma growth in vivo in a mouse model. (a) In order to evaluate the therapeutic effect of busulfan on osteosarcoma in vivo, we generated a mouse model by orthotopically injecting luciferase-transfected U2OS (U2OS-LUC) into the tibia of nude mice. One month later, busulfan was i.v. injected into the mice every other day for another month. (b,c) Tumor growth was monitored by bioluminescence imaging. We found a continuous growth of the implanted tumor in the control mice, but the tumor growth was significantly inhibited in the mice that received busulfan, shown by representative images (b), and by quantification (c). (d) TUNEL assay further confirmed that busulfan induced significant apoptosis of osteosarcoma cells in vivo. Scale bar = 40 μm.
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.

Bottom Line: Busulfan has been widely used to treat CML.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.

View Article: PubMed Central - PubMed

Affiliation: 169th Hospital, School of Medicine, Hunan Normal University, Changsha, China.

Show MeSH
Related in: MedlinePlus