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2016 ; 12
(5
): 3423-3428
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Celastrol negatively regulates cell invasion and migration ability of human
osteosarcoma via downregulation of the PI3K/Akt/NF-?B signaling pathway in vitro
#MMPMID27900015
Yu X
; Wang Q
; Zhou X
; Fu C
; Cheng M
; Guo R
; Liu H
; Zhang B
; Dai M
Oncol Lett
2016[Nov]; 12
(5
): 3423-3428
PMID27900015
show ga
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
cells in 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 ?B kinase ?/?, inhibitor of ?B ?, nuclear factor-?B (NF-?B subunit
p65) and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot
analysis. We observed that the PI3K/Akt/NF-?B 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-?B signaling pathway in vitro.