{"title":"[DTX2高表达促进奥沙利铂耐药结直肠癌细胞的增殖、侵袭和上皮-间质转化]。","authors":"Zhennan Ma, Fuquan Liu, Xuefeng Zhao, Xiaowei Zhang","doi":"10.12122/j.issn.1673-4254.2025.04.18","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The IC<sub>50</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 4","pages":"829-836"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037280/pdf/","citationCount":"0","resultStr":"{\"title\":\"[High expression of DTX2 promotes proliferation, invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells].\",\"authors\":\"Zhennan Ma, Fuquan Liu, Xuefeng Zhao, Xiaowei Zhang\",\"doi\":\"10.12122/j.issn.1673-4254.2025.04.18\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The IC<sub>50</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":18962,\"journal\":{\"name\":\"南方医科大学学报杂志\",\"volume\":\"45 4\",\"pages\":\"829-836\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037280/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"南方医科大学学报杂志\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.12122/j.issn.1673-4254.2025.04.18\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"南方医科大学学报杂志","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.12122/j.issn.1673-4254.2025.04.18","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
[High expression of DTX2 promotes proliferation, invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells].
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.
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