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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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Related in: MedlinePlus

Upregulating the microRNA-200 (miR-200) family, or inhibiting ZEB1 and ZEB2, partly mimicked the effect of busulfan in osteosarcoma cell lines. (a) U2OS cells were transfected with mimics of miR-200a, miR-200b, miR-200b, miR-141, and miR-429 to upregulate miRNAs. The percentage of viable cells, apoptosis, β-gal-positive cells, and 2'-7'-Dichlorodihydrofluorescein diacetate (DCF-DA) levels were assayed after 24 h. All data were normalized to negative control. (b) MG-63 cells were transfected with siRNA for ZEB1 and ZEB2 to downregulate the expression of ZEB1 and ZEB2. The percentage of viable cells, apoptosis, β-gal-positive cells, and DCF-DA levels were assayed after 24 h. All data were normalized to negative control (NC). *P < 0.05.
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fig04: Upregulating the microRNA-200 (miR-200) family, or inhibiting ZEB1 and ZEB2, partly mimicked the effect of busulfan in osteosarcoma cell lines. (a) U2OS cells were transfected with mimics of miR-200a, miR-200b, miR-200b, miR-141, and miR-429 to upregulate miRNAs. The percentage of viable cells, apoptosis, β-gal-positive cells, and 2'-7'-Dichlorodihydrofluorescein diacetate (DCF-DA) levels were assayed after 24 h. All data were normalized to negative control. (b) MG-63 cells were transfected with siRNA for ZEB1 and ZEB2 to downregulate the expression of ZEB1 and ZEB2. The percentage of viable cells, apoptosis, β-gal-positive cells, and DCF-DA levels were assayed after 24 h. All data were normalized to negative control (NC). *P < 0.05.

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.


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)

Upregulating the microRNA-200 (miR-200) family, or inhibiting ZEB1 and ZEB2, partly mimicked the effect of busulfan in osteosarcoma cell lines. (a) U2OS cells were transfected with mimics of miR-200a, miR-200b, miR-200b, miR-141, and miR-429 to upregulate miRNAs. The percentage of viable cells, apoptosis, β-gal-positive cells, and 2'-7'-Dichlorodihydrofluorescein diacetate (DCF-DA) levels were assayed after 24 h. All data were normalized to negative control. (b) MG-63 cells were transfected with siRNA for ZEB1 and ZEB2 to downregulate the expression of ZEB1 and ZEB2. The percentage of viable cells, apoptosis, β-gal-positive cells, and DCF-DA levels were assayed after 24 h. All data were normalized to negative control (NC). *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig04: Upregulating the microRNA-200 (miR-200) family, or inhibiting ZEB1 and ZEB2, partly mimicked the effect of busulfan in osteosarcoma cell lines. (a) U2OS cells were transfected with mimics of miR-200a, miR-200b, miR-200b, miR-141, and miR-429 to upregulate miRNAs. The percentage of viable cells, apoptosis, β-gal-positive cells, and 2'-7'-Dichlorodihydrofluorescein diacetate (DCF-DA) levels were assayed after 24 h. All data were normalized to negative control. (b) MG-63 cells were transfected with siRNA for ZEB1 and ZEB2 to downregulate the expression of ZEB1 and ZEB2. The percentage of viable cells, apoptosis, β-gal-positive cells, and DCF-DA levels were assayed after 24 h. All data were normalized to negative control (NC). *P < 0.05.
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.

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