title: Histone deacetylase inhibitor sodium butyrate suppresses proliferation and promotes apoptosis in osteosarcoma cells by regulation of the MDM2-p53 signaling.
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.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Chuhai
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Boyi
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Binwei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
keywords: MDM2–p53 feedback loop; histone deacetylase inhibitor; osteosarcoma; sodium butyrate