Celecoxib Inhibits β-Catenin-Dependent Survival of the Human Osteosarcoma MG-63 Cell Line

Xia, Jing; Pei, Ling; Jp, Zhuang; Y, Ji; Xu, GP; Zp, Zhang; N, Li; Jl, Yan

doi:10.1177/147323001003800411

Cited by 38 publications

(27 citation statements)

References 29 publications

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“…Therefore, GSK3β has been identified as a tumor suppressor that is frequently inactivated in various tumors (42). However, studies have provided evidence that the exact role of GSK3β in tumorigenesis of human OS is controversial (43)(44)(45)(46). In the present study, we explored the effect of ORI on GSK-3β and found that the total GSK-3β protein level was significantly elevated in response to the treatment with ORI.…”

Section: Discussionmentioning

confidence: 79%

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Liu

Zhang

et al. 2014

International Journal of Oncology

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Abstract. It has been reported that oridonin (ORI) can inhibit proliferation and induce apoptosis in various types of cancer cell lines. However, the exact mechanism for this function remains unclear. In this study, we investigated the proliferation inhibitory effect of ORI on human osteosarcoma (OS) 143B cells and dissected the possible molecular mechanism(s) underlying this effect. We demonstrated that ORI can inhibit proliferation, induce apoptosis and arrest the cell cycle in 143B cells. Using luciferase reporter assay, we found that the Wnt/β-catenin signaling was inhibited in 143B cells by ORI. Accordingly, the total protein levels and nuclear translocation of β-catenin were reduced by ORI treatment. ORI increased glycogen synthase kinase 3β (GSK3β) activity and upregulated Dickkopf-1 (Dkk-1) expression. We found that Dkk-1 overexpression or β-catenin knockdown can potentiate the proliferation inhibitory effect of ORI in 143B cells, while β-catenin overexpression attenuated this effect. Using the xenograft tumor model of human OS, we demonstrated that ORI effectively inhibited the growth of tumors. Histological examination showed that ORI inhibited cancer cell proliferation, decreased the expression of PNCA and β-catenin. Our findings suggest that ORI can inhibit 143B OS cell proliferation by downregulating Wnt/β-catenin signal transduction, which may be mediated by upregulating the Dkk-1 expression and/ or enhancing the function of GSK3β. Therefore, ORI can be potentially used as an effective adjuvant agent for the clinical management of OS.

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Section: Discussionmentioning

confidence: 79%

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Liu

Zhang

et al. 2014

International Journal of Oncology

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“…Overexpression of bone morphogenetic protein 9 decreased the expression levels of β-catenin mRNA and protein, downregulated its downstream proteins c-myc and osteoprotegerin, and suppressed the phosphorylation level of GSK-3β (Ser 9) in osteosarcoma cells (37). In addition, a previous study revealed that celecoxib, a cyclooxygenase (COX)-2 inhibitor, exerted an inhibitory effect on the viability of MG63 cells in a time- and dose-dependent manner, by inhibiting the expression of β-catenin and c-myc, and encoding cyclin D1 (38). This suggests that β-catenin is required for MG63 cell survival and the Wnt/β-catenin pathway is a COX-2-independent target for non-steroidal anti-inflammatory drugs in osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

Yao

Miao

et al. 2016

Oncology Letters

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There is increasing evidence that microRNAs (miRs) are implicated in tumor development and progression; however, their specific roles in osteosarcoma are not well understood. The aim of the present study was to investigate the role of miR-506 in the pathogenesis of osteosarcoma. The expression levels of miR-506 and astrocyte elevated gene-1 (AEG-1) mRNA were detected using quantitative polymerase chain reaction, and the protein levels of AEG-1, β-catenin, c-myc and cyclin D1 were determined using western blot analysis. The effects of miR-506 and AEG-1 on cell viability, colony forming ability and apoptosis were assessed using MTT assay, colony formation assay, and flow cytometry, respectively. Lucifer reporter assays were used to demonstrate whether AEG-1 is a direct target of miR-506. The present study identified that miR-506 was downregulated in osteosarcoma tissues and cells. Overexpression of miR-506 suppressed the proliferation and induced apoptosis in osteosarcoma cells in vitro and inhibited tumor formation in vivo. Overexpression of miR-506 significantly inhibited the luciferase activity of AEG-1 with a wild-type 3′-untranslated region, providing clear evidence that AEG-1 was a direct and functional downstream target of miR-506. Similar to the overexpression of miR-506, downregulation of AEG-1 lead to an inhibitory effect on osteosarcoma in vitro. Furthermore, overexpression of miR-506 or downregulation of AEG-1 inhibited the Wnt/β-catenin signaling pathway, and inhibition of this pathway by β-catenin small interfering RNA or CGP049090, a small molecule inhibitor, suppressed cell proliferation and induced apoptosis in vitro. Overall, the present data indicated that miR-506 functions as a tumor suppressor by targeting AEG-1 in osteosarcoma via the regulation of the Wnt/β-catenin signaling pathway.

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“…Interestingly, the Wnt/b-catenin pathway has been reported to be a target of COX-2 inhibitors. 52 mTOR is another kinase to be considered. Indeed, the mTOR pathway is also implicated in G 1 /S transition by inhibiting p27 expression and by stimulating cyclin D1 expression.…”

Section: Cox-2 Inhibitors Impair C-myc Expressionmentioning

confidence: 99%

Cox-2 inhibitors induce early c-Myc downregulation and lead to expression of differentiation markers in leukemia cells

Sobolewski

Cerella²,

Dicato³

et al. 2011

Cell Cycle

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Celecoxib Inhibits β-Catenin-Dependent Survival of the Human Osteosarcoma MG-63 Cell Line

Abstract: Cyclo-oxygenase (COX)-

Cited by 38 publications

References 29 publications

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

Cox-2 inhibitors induce early c-Myc downregulation and lead to expression of differentiation markers in leukemia cells

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