Imipramine-mediated Suppression of EGFR Signaling Attenuates Invasive and Progressive Abilities of Hepatocellular Carcinoma Cells.

IF 1.7 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-12-01 DOI:10.21873/anticanres.17360

Chun-Yu Fu, Pen-An Liao, Tzu-Hsiang Lin, Fei-Ting Hsu, Dai-Cheng Dong, Wei-Ting Chen

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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.

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丙咪嗪介导的EGFR信号抑制可减弱肝癌细胞的侵袭和进展能力。

背景/目的：肝细胞癌（HCC）是一种世界范围内死亡率高的原发性肝癌，需要有效的治疗策略。丙咪嗪显示了增强不同癌症标准治疗的潜力，突出了其在肿瘤学治疗方面的前景。本研究旨在探讨丙咪嗪对HCC的潜在调节作用。材料与方法：采用MTT法、流式细胞术、western blotting检测Huh7和Hep3B细胞的细胞毒性、凋亡、转移、抗凋亡和信号调控。结果：丙咪嗪显著诱导Huh7和Hep3B细胞的细胞毒性和膜联蛋白v活化，且呈时间和剂量依赖性。在机制上，丙咪嗪通过外源性（Fas-Fas-L）和内源性（线粒体）凋亡途径诱导HCC细胞的细胞毒性和凋亡。它还能抑制HCC转移，抑制表皮生长因子受体(EGFR)/有丝分裂原激活的细胞外信号调节激酶(MEK)/细胞外信号调节激酶（ERKs）信号传导。结论：丙咪嗪有望提高HCC患者的治疗效果，并在体外HCC模型中靶向EGFR/MEK/ERK信号通路，从而增强标准治疗的有效性。

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

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

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.