Effective targeting of E2F1 transcription factor via siRNA gene electrotransfer in HT-29 colorectal carcinoma xenografts

IF 4.8 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioelectrochemistry Pub Date : 2025-04-25 DOI:10.1016/j.bioelechem.2025.108994

Tanja Jesenko , Simona Kranjc Brezar , Ziva Pisljar , Tim Bozic , Bostjan Markelc , Monica Cazzato , Gabriele Grassi , Maja Cemazar

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引用次数: 0

Abstract

Colorectal cancer (CRC) remains a significant global health concern, with survival outcomes heavily dependent on the stage at diagnosis. Targeted therapies offer a promising approach to improve patient outcomes, particularly by addressing molecular drivers of tumor progression. One such target is the E2F1 transcription factor, a key regulator of the cell cycle and a contributor to proliferation, differentiation, apoptosis, metastasis, and chemoresistance in CRC. Previous studies have demonstrated the efficacy of E2F1 silencing via siRNA-loaded nanoliposomes in reducing tumor cell growth, but challenges such as immunogenicity and off-target effects have limited their in vivo application. In this study, we evaluated the potential of gene electrotransfer (GET) as a non-viral delivery system for delivery of therapeutic siRNA targeting E2F1 in the HT-29 CRC model. In vitro experiments showed effective silencing of E2F1 expression and a significant reduction in HT-29 cell survival. Subsequent in vivo studies confirmed the therapeutic potential of siE2F1 GET, with results demonstrating tumor growth delay, decreased proliferation, and increased necrosis in the tumors. This study establishes proof-of-principle for targeting E2F1 in CRC using GET, showcasing its versatility and therapeutic potential.

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通过siRNA基因电转移在HT-29结直肠癌异种移植物中有效靶向E2F1转录因子

结直肠癌（CRC）仍然是一个重要的全球健康问题，其生存结果严重依赖于诊断时的阶段。靶向治疗提供了一种有希望的方法来改善患者的预后，特别是通过解决肿瘤进展的分子驱动因素。其中一个靶标是E2F1转录因子，它是细胞周期的关键调节因子，也是CRC中增殖、分化、凋亡、转移和化疗耐药的贡献者。先前的研究已经证明了通过负载sirna的纳米脂质体沉默E2F1可以降低肿瘤细胞的生长，但免疫原性和脱靶效应等挑战限制了它们在体内的应用。在这项研究中，我们评估了基因电转移（GET）作为一种非病毒递送系统在HT-29 CRC模型中递送靶向E2F1的治疗性siRNA的潜力。体外实验显示，E2F1表达有效沉默，HT-29细胞存活率显著降低。随后的体内研究证实了siE2F1 GET的治疗潜力，结果显示肿瘤生长延迟，增殖减少，肿瘤坏死增加。本研究建立了使用GET靶向结直肠癌E2F1的原理证明，展示了其多功能性和治疗潜力。

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

Bioelectrochemistry 生物-电化学

CiteScore

9.10

自引率

6.00%

发文量

238

审稿时长

38 days

期刊介绍： An International Journal Devoted to Electrochemical Aspects of Biology and Biological Aspects of Electrochemistry Bioelectrochemistry is an international journal devoted to electrochemical principles in biology and biological aspects of electrochemistry. It publishes experimental and theoretical papers dealing with the electrochemical aspects of: • Electrified interfaces (electric double layers, adsorption, electron transfer, protein electrochemistry, basic principles of biosensors, biosensor interfaces and bio-nanosensor design and construction. • Electric and magnetic field effects (field-dependent processes, field interactions with molecules, intramolecular field effects, sensory systems for electric and magnetic fields, molecular and cellular mechanisms) • Bioenergetics and signal transduction (energy conversion, photosynthetic and visual membranes) • Biomembranes and model membranes (thermodynamics and mechanics, membrane transport, electroporation, fusion and insertion) • Electrochemical applications in medicine and biotechnology (drug delivery and gene transfer to cells and tissues, iontophoresis, skin electroporation, injury and repair). • Organization and use of arrays in-vitro and in-vivo, including as part of feedback control. • Electrochemical interrogation of biofilms as generated by microorganisms and tissue reaction associated with medical implants.