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Bazedoxifene Suppresses the Growth of Osteosarcoma Cells by Inhibiting IL-6 and IL-11/GP130 Signaling Pathway

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单位： [1]Department of Pediatric Surgery, Tongji Hospital. [2]The Research Institute at Nationwide Children's Hospital, The Ohio State University. [3]Department of Hematology & Cancer Biology Research Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,P.R. China. [4]The Ohio State University Comprehensive Cancer Center, Columbus, OH. [5]Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD.

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关键词： bazedoxifene osteosarcoma GP130 STAT3

摘要：

Osteosarcoma is the most common primary bone tumor. Using the multiple ligands simultaneous docking method, we found that bazedoxifene could bind to the GP130 D1 domain. We then demonstrated that bazedoxifene can decrease cell viability and cell migration of osteosarcoma cells by inhibiting interleukin 6 (IL-6) and IL-11/GP130 signaling. Consistently, treatment with IL-6 or IL-11 antibody or knockdown of GP130 by siRNA silenced the activation of STAT3, ERK, and AKT. Similarly, recombinant IL-6 and IL-11 proteins antagonized the inhibitory effect of bazedoxifene on osteosarcoma cells. Finally, the combinational treatment of temsirolimus and bazedoxifene synergistically suppressed osteosarcoma development in vitro and in vivo. Our findings suggest that bazedoxifene directly prompts the deactivation of GP130 and inhibits the osteosarcoma progression in vitro and in vivo. Therefore, bazedoxifene could be effectively applied as a therapeutic drug for human osteosarcoma in the future.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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出版当年[2023]版：

大类 | 4 区医学

小类 | 4 区血液学 4 区肿瘤学 4 区儿科

最新[2025]版：

大类 | 4 区医学

小类 | 4 区血液学 4 区肿瘤学 4 区儿科

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出版当年[2022]版：

Q4 HEMATOLOGY Q4 ONCOLOGY Q4 PEDIATRICS

最新[2023]版：

Q3 PEDIATRICS Q4 HEMATOLOGY Q4 ONCOLOGY

影响因子： 0.9 最新[2023版] 1 最新五年平均 1.2 出版当年[2022版] 1.2 出版当年五年平均 1.17 出版前一年[2021版] 0.9 出版后一年[2023版]

第一作者：

第一作者单位： [1]Department of Pediatric Surgery, Tongji Hospital. [2]The Research Institute at Nationwide Children's Hospital, The Ohio State University.

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通讯机构： [1]Department of Pediatric Surgery, Tongji Hospital. [2]The Research Institute at Nationwide Children's Hospital, The Ohio State University. [5]Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD. [*1]1095 Jiefang Avenue, Wuhan, Hubei 430030, China [*2]220 Arch Street, Baltimore, MD 21201-1531

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