DNMT1 reduces cisplatin sensitivity partially through downregulating FOXO3a in ovarian cancer cells.

IF 1.8 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2025-09-15 DOI:10.1080/1120009X.2025.2556581

Chong Guo, Qingqing Yu, Fangzhou Li, Bailu Zhang, Yucheng Wang, Chao Zhang, Boyu Du, Ruifang An

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引用次数: 0

Abstract

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.

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DNMT1部分通过下调卵巢癌细胞中的FOXO3a来降低顺铂敏感性。

大多数卵巢癌（OC）患者在接受治疗时产生顺铂耐药性。生物信息学分析将DNA甲基转移酶1 （DNMT1）与卵巢癌患者的化疗耐药发展以及FOXO3a表达联系起来。体外研究结果显示，顺铂治疗可诱导DNMT1表达。敲低DNMT1可降低顺铂的IC50。顺铂治疗可降低OC细胞中FOXO3a的表达。而在DNMT1敲低的OC细胞中，顺铂可诱导FOXO3a表达。DNMT1可能通过启动子甲基化抑制FOXO3a的表达。FOXO3a过表达可显著提高顺铂敏感性。荟萃分析还揭示了对OC患者预后的相反影响：高表达DNMT1是总生存和无病生存的危险因素，而高表达FOXO3a可能提高高级别浆液性腺癌OC患者的5年生存率。因此，我们的研究结果表明DNMT1可以通过调节FOXO3a部分降低OC细胞的顺铂敏感性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

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.