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Histone deacetylase inhibitor sodium butyrate suppresses proliferation and promotes apoptosis in osteosarcoma cells by regulation of the MDM2–p53 signaling

Authors Xie C, Wu B, Chen B, Shi Q, Guo J, Fan Z, Huang Y

Received 30 January 2016

Accepted for publication 15 April 2016

Published 4 July 2016 Volume 2016:9 Pages 4005—4013

DOI https://doi.org/10.2147/OTT.S105418

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Chuhai Xie, Boyi Wu, Binwei Chen, Qunwei Shi, Jianhong Guo, Ziwen Fan, Yan Huang

Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China

Abstract: Histone deacetylase inhibitors have been reported to induce tumor cell growth arrest, differentiation, and apoptosis. This study aimed to investigate the effects of one histone deacetylase inhibitor – sodium butyrate (SB) – on osteosarcoma (OS) cell proliferation and apoptosis and also the molecular mechanisms by which SB exerts regulatory effects on OS cells. U2OS and MG63 cells were treated with SB at various concentrations. Then, cell proliferation and apoptosis were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and flow cytometry assays, respectively; the expression of Ki67, Bax, Bcl-2, MDM2, and p53 proteins was determined by using Western blot assay. The results showed that SB suppressed proliferation in a concentration-dependent manner and promoted apoptosis of OS cells. In addition, SB enhanced p53 expression and decreased MDM2 expression, indicating that SB can regulate MDM2–p53 feedback loop. p53 inhibited proliferation and promoted apoptosis, whereas MDM2 promoted proliferation and suppressed apoptosis, which indicated that functional effect of SB on OS cell lines at least in part depended on the MDM2–p53 signaling. We also explored the effect of SB on OS cells in vivo and found that SB suppressed the growth of OS cells with no noticeable effect on activity and body weight of mice in vivo. These findings will offer new clues for OS development and progression and offer SB as a potent targeted agent for OS treatment.

Keywords: osteosarcoma, histone deacetylase inhibitor, sodium butyrate, MDM2–p53 feedback loop
 

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