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| 1 | Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions显示文摘Objective:The aim of this study was to investigate the effects of plumbagin(PL),a naphthoquinone derived from the medicinal plant plumbago zeylanica,on the invasion and migration of human breast cancer cells.Methods:Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plumbagin for 24 h.The effects of plumbagin on the migration and invasion were observed by a transwell method.The expressions of IL-1α,IL-1β,IL-6,IL-8,TGF-β,TNFα,MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR.MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes.The activation of STAT3 was detected by western blot.Following this analysis,STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA.mRNA levels of IL-1α,TGF-β,MMP-2 and MMP-9 were then detected.Consequently,MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model.The mice were injected intraperitoneally with plumbagin.Non-invasive in vivo monitoring,X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo.Results:The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α,TGF-β,MMP-2 and MMP-9.Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells.The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α,TGF-β,MMP-2 and MMP-9.In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases,as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions.Conclusions:Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1α,TGF-β,MMP-2 and MMP-9. | Wei Yan Bing Tu Yun-yun Liu Ting-yu Wang Han Qiao Zan-jing Zhai Hao-wei Li Ting-ting Tang | 2013 | Bone Research2013，1，4： | 5 |
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