Chong Guo, Qingqing Yu, Fangzhou Li, Bailu Zhang, Yucheng Wang, Chao Zhang, Boyu Du, Ruifang An
{"title":"DNMT1部分通过下调卵巢癌细胞中的FOXO3a来降低顺铂敏感性。","authors":"Chong Guo, Qingqing Yu, Fangzhou Li, Bailu Zhang, Yucheng Wang, Chao Zhang, Boyu Du, Ruifang An","doi":"10.1080/1120009X.2025.2556581","DOIUrl":null,"url":null,"abstract":"<p><p>Most individuals with ovarian cancer (OC) develop cisplatin resistance while undergoing treatment. Bioinformatic analysis has linked DNA Methyltransferase 1 (DNMT1) to chemoresistance development as well as FOXO3a expression in OC patients. In vitro study results revealed cisplatin treatment could induce DNMT1 expression. Knocking down of DNMT1 could decrease the IC<sub>50</sub> of cisplatin. Treatment with cisplatin may reduce FOXO3a expression in OC cells. While in DNMT1 knockdown OC cells, treatment with cisplatin could induce FOXO3a expression. DNMT1 might suppress FOXO3a expression by promoter methylation. FOXO3a overexpression could significantly enhance cisplatin sensitivity. Meta-analysis also revealed opposite effects on OC patients- prognosis: higher expression of DNMT1 is a risk factor for both overall survival and disease-free survival, while high FOXO3a may improve the 5-year survival rate in high-grade serous adenocarcinoma OC patients. Therefore, our results indicated DNMT1 could reduce cisplatin sensitivity in OC cells partially via regulating FOXO3a.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-13"},"PeriodicalIF":1.8000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DNMT1 reduces cisplatin sensitivity partially through downregulating FOXO3a in ovarian cancer cells.\",\"authors\":\"Chong Guo, Qingqing Yu, Fangzhou Li, Bailu Zhang, Yucheng Wang, Chao Zhang, Boyu Du, Ruifang An\",\"doi\":\"10.1080/1120009X.2025.2556581\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Most individuals with ovarian cancer (OC) develop cisplatin resistance while undergoing treatment. Bioinformatic analysis has linked DNA Methyltransferase 1 (DNMT1) to chemoresistance development as well as FOXO3a expression in OC patients. In vitro study results revealed cisplatin treatment could induce DNMT1 expression. Knocking down of DNMT1 could decrease the IC<sub>50</sub> of cisplatin. Treatment with cisplatin may reduce FOXO3a expression in OC cells. While in DNMT1 knockdown OC cells, treatment with cisplatin could induce FOXO3a expression. DNMT1 might suppress FOXO3a expression by promoter methylation. FOXO3a overexpression could significantly enhance cisplatin sensitivity. Meta-analysis also revealed opposite effects on OC patients- prognosis: higher expression of DNMT1 is a risk factor for both overall survival and disease-free survival, while high FOXO3a may improve the 5-year survival rate in high-grade serous adenocarcinoma OC patients. Therefore, our results indicated DNMT1 could reduce cisplatin sensitivity in OC cells partially via regulating FOXO3a.</p>\",\"PeriodicalId\":15338,\"journal\":{\"name\":\"Journal of Chemotherapy\",\"volume\":\" \",\"pages\":\"1-13\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1120009X.2025.2556581\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1120009X.2025.2556581","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
DNMT1 reduces cisplatin sensitivity partially through downregulating FOXO3a in ovarian cancer cells.
Most individuals with ovarian cancer (OC) develop cisplatin resistance while undergoing treatment. Bioinformatic analysis has linked DNA Methyltransferase 1 (DNMT1) to chemoresistance development as well as FOXO3a expression in OC patients. In vitro study results revealed cisplatin treatment could induce DNMT1 expression. Knocking down of DNMT1 could decrease the IC50 of cisplatin. Treatment with cisplatin may reduce FOXO3a expression in OC cells. While in DNMT1 knockdown OC cells, treatment with cisplatin could induce FOXO3a expression. DNMT1 might suppress FOXO3a expression by promoter methylation. FOXO3a overexpression could significantly enhance cisplatin sensitivity. Meta-analysis also revealed opposite effects on OC patients- prognosis: higher expression of DNMT1 is a risk factor for both overall survival and disease-free survival, while high FOXO3a may improve the 5-year survival rate in high-grade serous adenocarcinoma OC patients. Therefore, our results indicated DNMT1 could reduce cisplatin sensitivity in OC cells partially via regulating FOXO3a.
期刊介绍：
The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy.
The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs.
Specific areas of focus include, but are not limited to:
· Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents;
· Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy;
· Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents;
· The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs;
· Drug interactions in single or combined applications;
· Drug resistance to antimicrobial and anticancer drugs;
· Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research;
· Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs;
· Pharmacogenetics and pharmacogenomics;
· Precision medicine in infectious disease therapy and in cancer therapy;
· Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.
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