关键词:

宫颈癌干细胞, 放化疗抵抗, SFRP1, Wnt/β?catenin通路

Abstract:

Objective To explore the role of SFRP1/Wnt/β⁃catenin signaling pathway in cervical cancer stem cells. Methods Flow cytometry was performed to sort SP cells and NSP cells in SiHa cells. The in vivo and in vitro functional assays were conducted to verify the ability of proliferation，cloning，spheroidization and subcuta⁃ neous tumor formation between SP and NSP cells，and stem cell markers，including CD133，CD44 and Nanog， were detected by Western blot assay. After treatment with radiotherapy and chemotherapy，the ability of cell prolif⁃ eration and clone formation was determined. Protein expression of SFRP1，activation of Wnt/β⁃catenin signal were detected，expression of β ⁃catenin was detected by immunofluorescence assay，and the secretion of SFRP1 was detected by ELISA. Results The proliferation，clone formation，spheroidization and subcutaneous tumor formation abilities of SP cells were significantly stronger than those in NSP cells，and the level of stem cell markers of SP cells were significantly higher than those in NSP cells.After radiotherapy and chemotherapy，the proliferation and cloning abilities of SP cells were significantly stronger than those in NSP cells. The expression of SFRP1 in SP cells was significantly higher than that in NSP cells，while the concentration of secreted SFRP1 in SP cells was signifi⁃ cantly lower than that in NSP cells. Wnt/β⁃catenin pathway was activated in SP cells and β⁃catenin was significantly expressed in the nucleus of SP cells. Conclusion Cervical cancer stem cells may activate the Wnt/β⁃catenin path⁃ way by reducing the secretion of SFRP1，promoting their proliferation，cloning and subcutaneous tumor formation， and enhancing their resistance to radiotherapy and chemotherapy. 

Key words:

cervical cancer stem cells, radiotherapy and chemotherapy resistance, SFRP1, Wnt/β-catenin pathway