High expression of DTX2 promotes proliferation,invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells

MA Zhennan; LIU Fuquan; ZHAO Xuefeng; ZHANG Xiaowei

doi:10.12122/j.issn.1673-4254.2025.04.18

Abstract：Objective To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells(CRC/OXA cells).Methods CCK8 assay was used to determine the inhibition rate of oxaliplatin-treated CRC cells.A CRC/OXA cell line was constructed,in which DTX2 expression level was detected.The cells were transfected with a DTX2-shRNA plasmid or co-transfected with DTX2-shRNA and pcDNA-Notch2,and the changes in cell proliferation,migration and invasion ability were evaluated using plate cloning assay,scratch assay and Transwell invasion assay.The expression levels of Notch2,NICD and epithelial-mesenchymal transition(EMT)proteins of the transfected cells were detected with Western blotting.In a nude mouse model bearing SW620/OXA cell xenografts,the effects of DTX2 knockdown and Notch2 overexpression in the implanted cells on tumor growth and protein expressions were tested.Results The IC50 of oxaliplatin was 6.00 μmol/L in SW620 cells and 8.00 μmol/L in LoVo cells.CRC/OXA cells showed a significantly increased expression of DTX2.DTX2 knockdown in CRC/OXA cells significantly inhibited cell proliferation,migration and invasion,and these effects were reversed by co-transfection of the cells with pcDNA-Notch2.DTX2 knockdown significantly reduced the expression levels of Notch2,NICD and vimentin proteins and increased E-cadherin expression in CRC/OXA cells,and co-transfection with pcDNA-Notch2 potently attenuated the changes in these proteins.In the tumor-bearing mice,DTX2 overexpression obviously promoted the growth of SW620/OXA cell xenograft,enhanced the protein expressions of Notch2,NICD and vimentin,and lowered the expression of E-cadherin.Conclusion High expression of DTX2 promotes proliferation,migration,invasion and EMT of CRC/OXA cells through the Notch2 signaling pathway,suggesting the potential of DTX2 as a target to improve the efficacy of oxaliplatin.