Down-regulation of S100A9 inhibits osteosarcoma cell growth through inactivating MAPK and NF-κB signaling pathways

BMC Cancer

Research Article

Xi Zhang¹  Ning Huang²  Ying Jin³  Si Cheng⁴  Dianming Jiang⁴  Quanhe Qiu⁴ 

[1] Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China;Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China;Institute of Life Sciences,Chongqing Medical University, Chongqing, PR China;Department of Orthodontics, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, WestChina School of Stomatology, Sichuan University, Chongqing, PR China;Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China;

关键词: S100A9;    Osteosarcoma;    Proliferation;    Invasion;    Tumorigenesis;    MAPK;    NF-κB;   

DOI  :  10.1186/s12885-016-2294-1

 received in 2015-06-13, accepted in 2016-03-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundOsteosarcoma (OS) is well-known for poor prognosis due to its high incidence of proliferation and metastasis. Researches have provided valuable insights into the tumorigenesis of S100A9 in some cancers. We aimed to understand the expression level, functions and mechanisms of S100A9 in human osteosarcoma for the first time.MethodsThe expression of S100A9 protein was detected in 120 human osteosarcoma tissues and 40 normal human bone tissues using tissue microarrays analysis. The knockdown of S100A9 induced by RNA interference (RNAi) method in three osteosarcoma cell lines (U2OS, 143B, MG63) was applied to analyze the effects of S100A9 on cell proliferation, cell cycle distribution, migration, invasion and xenotransplanted tumors. Moreover, MAPK-ERK1/2, MAPK-p38, NF-κB-p65, NF-κB-p50, p21, p27, CDK2 and CDK4 were tested.ResultsThe expression of S100A9 was increased in human osteosarcoma issues and was positively correlated with clinical classification and survival rate. Down-regulation of S100A9 inhibited OS cellular proliferation, migration, invasion and cell cycle S phase in vitro and suppressed tumor formation in vivo with the reduction on PCNA and Ki67 proliferation index. Our data also demonstrated that knockdown of S100A9 repressed the protein levels of phospho-ERK1/2, phospho-p50, phospho-p65 except phospho-p38, and prompted up-regulation of p21 and p27 leading to inactivation of cyclin dependent kinase 2(CDK2) and cyclin dependent kinase 4(CDK4).ConclusionsS100A9 might be a significant role for predicting osteosarcoma prognosis and down-regulation of S100A9 could be used as a potential target for gene therapy.

【 授权许可】

CC BY   
© Cheng et al. 2016