Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway

通过下调 DKK1 和激活 WNT/β-catenin 通路,鉴定出 XD23 是骨肉瘤的有效抑制剂

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作者:Qian Xie, Yanni Shen, Yipei Yang, Jianhui Liang, Tailin Wu, Chun Hu, Yan Wang, Huiren Tao

Abstract

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-β/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease.

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