title: Celastrol negatively regulates cell invasion and migration ability of human osteosarcoma via downregulation of the PI3K/Akt/NF-κB signaling pathwayin vitro.
abstract: Osteosarcoma (OS) is a primary malignant tumor of the bone, with a tendency to metastasize early. Despite the advances in treatment options, more than 30% of patients develop distant metastases, and the prognosis of these patients with metastases is extremely poor. Celastrol has been demonstrated to manifest multiple pharmacological activities, including induction of apoptosis in numerous types of cancer cell lines. Our previous studies have also suggested that Celastrol is capable of inducing apoptosis of human osteosarcoma cells via the mitochondrial-dependent pathway. The purpose of this study was to investigate the effects of Celastrol on the migration and invasion of human osteosarcoma U-2OS cellsin vitro. Cell migration and invasion were investigated using wound healing and Boyden chamber Transwell assays. We observed that Celastrol suppressed cell invasion and migration in human osteosarcoma U-2OS cells. Furthermore, protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, inhibitor of κB kinase α/β, inhibitor of κB α, nuclear factor-κB (NF-κB subunit p65) and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot analysis. We observed that the PI3K/Akt/NF-κB signaling pathway was inhibited following Celastrol treatment. In addition, the expression levels of MMP-2 and -9 proteins were also reduced significantly following Celastrol treatment. Therefore, we confirmed that Celastrol suppressed osteosarcoma U-2OS cell metastasis via downregulation of the PI3K/Akt/NF-κB signaling pathwayin vitro.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Multidisciplinary Therapy Center of Musculoskeletal Tumor, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Runsheng
authors.initials: R
authors.lastname: Guo
authors.affiliation: Multidisciplinary Therapy Center of Musculoskeletal Tumor, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Hucheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
keywords: Celastrol; invasion; matrix metalloproteinases; migration; osteosarcoma; phosphatidylinositol 3-kinase/Akt