三种耐吉西他滨人肝内胆管癌细胞系的建立和鉴定。

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-02-09 DOI:10.1038/s41598-025-89423-0

Jiandong Li, Yanxin Hu, Jiayao Zhang, Weiguang Zhang, Jianhua Yu, Baochun Lu

{"title":"三种耐吉西他滨人肝内胆管癌细胞系的建立和鉴定。","authors":"Jiandong Li, Yanxin Hu, Jiayao Zhang, Weiguang Zhang, Jianhua Yu, Baochun Lu","doi":"10.1038/s41598-025-89423-0","DOIUrl":null,"url":null,"abstract":"Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"4813"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808057/pdf/","citationCount":"0","resultStr":"{\"title\":\"Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines.\",\"authors\":\"Jiandong Li, Yanxin Hu, Jiayao Zhang, Weiguang Zhang, Jianhua Yu, Baochun Lu\",\"doi\":\"10.1038/s41598-025-89423-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.\",\"PeriodicalId\":21811,\"journal\":{\"name\":\"Scientific Reports\",\"volume\":\"15 1\",\"pages\":\"4813\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-02-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808057/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scientific Reports\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41598-025-89423-0\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-89423-0","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

肝内胆管癌（ICC）是一种预后差的高度恶性肝脏肿瘤，主要是由于化疗耐药。然而，ICC患者对吉西他滨（GEM）耐药的机制仍然知之甚少。在这项研究中，我们建立了三种gem耐药细胞模型，并通过评估细胞增殖、细胞周期阻滞和DNA损伤来评估它们的耐药性。与亲代细胞相比，gem抗性细胞对gem诱导的生长抑制表现出显著的耐受性，减少了细胞周期停滞，减少了DNA损伤。随后，我们探索了潜在的耐药机制，发现上皮-间质转化、PI3K/Akt、p53R2和IGF-1R等途径和靶点与ICC耐药没有显著相关性。有趣的是，我们的研究结果表明活性氧可能促进ICC对GEM的抗性。总之，我们描述了一个耐gem的ICC模型，该模型可用于研究替代耐药机制和探索新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

期刊介绍： We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.