Preliminary Study Of Denosumab Inhibiting Giant Cell Tumor Of Bone By STAT3 Signaling Pathway

Objective: To study the expression and significance of Stat3 signaling pathway and its downstream related molecules in the treatment of giant cell tumor with Denosumab.Methods: The expressions of Rank1,Stat3,Bcl-2 and Cyclin D1 in giant cell tumor of bone treated with and without Denosumab were detected by immunohistochemistry.The TUNEL method was used to detect apoptosis of tumor cells in paraffin sections with and without Denosumab.To analyze the mechanism of action of Stat3 and its downstream related molecules in the progression of giant cell tumor of bone,and to determine whether denosumab can promote the apoptosis of tumor cells.Results: 1.HE staining results: The giant cell tumor tissue treated with denosumab was mainly composed of tumor stromal cells and multinucleated osteoclast-like giant cells;after treatment with denosumab,the osteoclast-like giant cells disappeared and the residual part was fine.Long-form tumor stromal cells,a large number of reticular fibrous tissue and woven bone form and replace tumor tissue;2.Immunohistochemistry results: Rank1 is mainly expressed in tumor stromal cells,Stat3 is mainly expressed in multinucleated osteoclast cytoplasm and tumor stromal cells In the cell membrane,Bcl-2 is mainly expressed in the cytoplasm of multinucleated osteoclast-like giant cells,scattered in the nucleus,and Cyclin D1 is expressed in the nucleus of multinucleated osteoclast-like giant cells;The positive expression rates of Rank1,Stat3,Bcl-2 and Cyclin D1 in 30 cases of tumors without denosumab treatment were 70%,53%,77%,73%,respectively.After denosumab treatment the expression of Rankl in tumors was significantly reduced,and the expression of Stat3,Bcl-2 and Cyclin D1 molecules was not observed.3.Apoptosis test results: only a few tumor cells apoptosis were observed in giant cell tumors of bone treated with denosumab,and the residual tumor stromal cells after treatment with denosumab showed obvious apoptosis.Conclusion: Denosumab may inhibit the formation of multinucleated osteoclast-like giant cells and promote the apoptosis of tumor stromal cells by inhibiting Stat3 signaling pathway.