High expression of DTX2 promotes proliferation, invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells.
10.12122/j.issn.1673-4254.2025.04.18
- Author:
Zhennan MA
1
;
Fuquan LIU
1
;
Xuefeng ZHAO
1
;
Xiaowei ZHANG
1
Author Information
1. Department of Anorectal Surgery, Dalian University Affiliated Xinhua Hospital, Dalian 116021, China.
- Publication Type:Journal Article
- Keywords:
Nohch2 signaling pathway;
colorectal cancer;
deltex-2;
epithelial-mesenchymal transition;
oxaliplatin resistance
- MeSH:
Epithelial-Mesenchymal Transition;
Humans;
Cell Proliferation;
Oxaliplatin;
Colorectal Neoplasms/metabolism*;
Animals;
Drug Resistance, Neoplasm;
Receptor, Notch2/metabolism*;
Cell Line, Tumor;
Mice, Nude;
Cell Movement;
Organoplatinum Compounds/pharmacology*;
Neoplasm Invasiveness;
Mice
- From:
Journal of Southern Medical University
2025;45(4):829-836
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS: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.
