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

Autor:	Fu CY; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.; Department of Colon and Rectal Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C., Liao PA; School of Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.; Department of Radiology, Cathay General Hospital, Taipei, Taiwan, R.O.C., Lin TH; Department of Radiology, Cathay General Hospital, Taipei, Taiwan, R.O.C., Hsu FT; Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C., Dong DC; Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C., Chen WT; Department of Psychiatry, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.; wt820368@yahoo.com.tw.; Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan, R.O.C.; Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
Jazyk:	angličtina
Zdroj:	Anticancer research [Anticancer Res] 2024 Dec; Vol. 44 (12), pp. 5323-5335.
DOI:	10.21873/anticanres.17360
Abstrakt:	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. (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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