{"title":"Imipramine-mediated Suppression of EGFR Signaling Attenuates Invasive and Progressive Abilities of Hepatocellular Carcinoma Cells.","authors":"Chun-Yu Fu, Pen-An Liao, Tzu-Hsiang Lin, Fei-Ting Hsu, Dai-Cheng Dong, Wei-Ting Chen","doi":"10.21873/anticanres.17360","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality rates worldwide, necessitating effective therapeutic strategies. Imipramine demonstrates the potential to augment standard treatments of different cancers, highlighting its therapeutic promise in oncology. This study aimed to investigate the potential regulation of imipramine on HCC.</p><p><strong>Materials and methods: </strong>Cytotoxicity, apoptosis, metastasis, anti-apoptosis and signaling regulation were assessed in Huh7 and Hep3B cells using MTT assay, flow cytometry, and western blotting.</p><p><strong>Results: </strong>Imipramine markedly induced cytotoxicity and Annexin-V activation in Huh7 and Hep3B cells in a time and dose-dependent manner. Mechanistically, imipramine induced cytotoxicity and apoptosis in HCC cells via both extrinsic (Fas-Fas-L) and intrinsic (mitochondrial) apoptosis pathways. It also suppressed HCC metastasis and inhibited epidermal growth factor receptor (EGFR)/mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinases (ERKs) signaling.</p><p><strong>Conclusion: </strong>Imipramine shows promise in enhancing HCC treatment outcomes in patients and targets the EGFR/MEK/ERK signaling pathway in in vitro HCC models, thereby augmenting the effectiveness of standard therapies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5323-5335"},"PeriodicalIF":1.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17360","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background/aim: Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality rates worldwide, necessitating effective therapeutic strategies. Imipramine demonstrates the potential to augment standard treatments of different cancers, highlighting its therapeutic promise in oncology. This study aimed to investigate the potential regulation of imipramine on HCC.
Materials and methods: Cytotoxicity, apoptosis, metastasis, anti-apoptosis and signaling regulation were assessed in Huh7 and Hep3B cells using MTT assay, flow cytometry, and western blotting.
Results: Imipramine markedly induced cytotoxicity and Annexin-V activation in Huh7 and Hep3B cells in a time and dose-dependent manner. Mechanistically, imipramine induced cytotoxicity and apoptosis in HCC cells via both extrinsic (Fas-Fas-L) and intrinsic (mitochondrial) apoptosis pathways. It also suppressed HCC metastasis and inhibited epidermal growth factor receptor (EGFR)/mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinases (ERKs) signaling.
Conclusion: Imipramine shows promise in enhancing HCC treatment outcomes in patients and targets the EGFR/MEK/ERK signaling pathway in in vitro HCC models, thereby augmenting the effectiveness of standard therapies.
期刊介绍:
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.