Imipramine-induced Apoptosis and Metastasis Inhibition in Human Bladder Cancer T24 Cells Through EGFR/ERK/NF-κB Pathway Suppression.

IF 1.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

In vivo Pub Date : 2025-03-01 DOI:10.21873/invivo.13871

Wei-Shu Wang, Yu-Chang Liu, Tsai-Lin Lo, Fei-Ting Hsu, Chih-Hung Chiang

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引用次数: 0

Abstract

Background/aim: Bladder cancer is a prevalent malignancy, ranging from superficial forms to more aggressive types that invade the muscle and require extensive treatment. Imipramine, traditionally used as an antidepressant, has shown potential as an anti-cancer agent.

Materials and methods: In this study, human bladder cancer T24 cells were treated with varying concentrations of imipramine to evaluate its cytotoxic and apoptotic effects.

Results: Imipramine induced cytotoxicity in a dose-dependent manner, significantly increasing apoptosis as shown by Annexin-V/PI staining and TUNEL assay. The drug also up-regulated cleaved caspase-3 and down-regulated the anti-apoptotic factor XIAP. Moreover, imipramine activated both extrinsic/intrinsic apoptotic pathways, evidenced by the increased expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-9, along with mitochondrial dysfunction and ROS production. Imipramine inhibited the migration and invasion of bladder cancer cells, likely through the down-regulation of metastasis-related proteins and suppression of the EGFR/ERK/NF-[Formula: see text]B signaling pathway.

Conclusion: Imipramine could be a promising therapeutic agent for bladder cancer.

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丙咪帕明通过抑制EGFR/ERK/NF-κB通路诱导人膀胱癌T24细胞凋亡和转移

背景/目的：膀胱癌是一种普遍存在的恶性肿瘤，从表面的形式到侵入肌肉的更具侵袭性的类型，需要广泛的治疗。丙咪嗪，传统上用作抗抑郁药，已经显示出作为抗癌剂的潜力。材料和方法：本研究采用不同浓度丙咪嗪处理膀胱癌T24细胞，观察其细胞毒性和细胞凋亡作用。结果：丙咪嗪诱导细胞毒性呈剂量依赖性，Annexin-V/PI染色和TUNEL实验显示，丙咪嗪显著增加细胞凋亡。该药物还上调了裂解型caspase-3，下调了抗凋亡因子XIAP。此外，丙咪嗪激活了外源性/内源性凋亡途径，Fas、FasL、cleaved caspase-8和cleaved caspase-9的表达增加，以及线粒体功能障碍和ROS的产生证明了这一点。丙咪丙胺抑制膀胱癌细胞的迁移和侵袭，可能是通过下调转移相关蛋白和抑制EGFR/ERK/NF- B信号通路来实现的。结论：丙咪嗪是治疗膀胱癌的理想药物。

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

In vivo 医学-医学：研究与实验

CiteScore

4.20

自引率

4.30%

发文量

330

审稿时长

3-8 weeks

期刊介绍： IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management. The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.