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Effect of Bone Morphogenetic Protein 4 in the Human Brain Glioma Cell Line U251

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Abstract

The role of bone morphogenetic protein 4 (BMP4) in gliomas is not clear. We hypothesized that BMP4 inhibits proliferation in the brain glioma cell line U251 through a signaling pathway involving BMP4 and the mothers against decapentaplegic homolog 4 (SMAD4) protein. We exposed U251 cells to Adriamycin (1 g) for 48 h; cell proliferation (MTT assay), expression of BMP4 and SMAD4 (mRNA: qPCR; protein: Western blot) were studied. We further altered expression of BMP4 by overexpression or siRNA silencing, and documented cell responses to Adriamycin. Proliferation of U251 cells was significantly inhibited upon exposure to Adriamycin. This inhibition was associated with increased expression of BMP4. Further, proliferation of U251 cells was inhibited when BMP4 was overexpressed. BMP4 expression negatively correlated with expression of SMAD4, such that elevated levels of BMP4 were associated with decreased expression of SMAD4 and vice versa. The Adriamycin-induced inhibition of proliferation of U251 cells was attenuated when BMP4 was knocked down by siRNA. To conclude, BMP4 is associated with inhibition of proliferation of U251 cells; the effects of BMP4 involve the BMP4-Smad signaling pathway. BMP4 has a potential as a target for glioma therapy.

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Acknowledgments

The authors wish to thank Dr. Baiqu Huang for his kind gift of BMP4 plasmid. This study was funded by The National Natural Science Foundation of China (30772223).

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Correspondence to Qianxue Chen.

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Liu, B., Tian, D., Yi, W. et al. Effect of Bone Morphogenetic Protein 4 in the Human Brain Glioma Cell Line U251. Cell Biochem Biophys 58, 91–96 (2010). https://doi.org/10.1007/s12013-010-9095-y

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