文章：

铁死亡增强溶瘤腺病毒KD01对抗癌症的治疗潜力

Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer 

原文发布日期：2025-03-03 

英文摘要：

Oncolytic virotherapy has emerged as a promising strategy for cancer treatment by selectively targeting and lysing tumor cells. However, its efficacy is often limited in certain tumor types due to multiple factors. This study explores the combination of oncolytic adenoviruses with Erastin, a potent ferroptosis inducer, to enhance antitumor efficacy in oncolytic virus-insensitive cancer cell lines. In vitro experiments demonstrated that Erastin significantly increased the cytotoxicity of oncolytic virotherapy, leading to greater inhibition of cell proliferation and elevated rates of cell death compared to monotherapies. The combination treatment further promoted ferroptosis, as evidenced by increased reactive oxygen species (ROS) levels, enhanced lipid peroxidation, and disrupted redox homeostasis. RNA sequencing identified the downregulation of Dickkopf-1 (DKK1) as a key mediator of the enhanced ferroptotic effect. Restoring the expression of DKK1 partially mitigated the cytotoxic effects of the combination therapy, highlighting its crucial role in mediating the enhanced ferroptosis-induced oncolytic virotherapy efficacy. In vivo studies further validated these findings, demonstrating that the combined treatment significantly reduced tumor growth without inducing notable toxicity. This novel therapeutic approach has great potential to enhance the efficacy of oncolytic virotherapy in cancers resistant to oncolytic viruses by inducing ferroptosis. Further investigation in clinically relevant models is warranted to fully elucidate the underlying mechanisms and to optimize this combination strategy for potential clinical applications. 

摘要翻译：

溶瘤病毒疗法通过选择性靶向和裂解肿瘤细胞，已成为一种颇具前景的癌症治疗策略。然而，受多重因素影响，该疗法在某些肿瘤类型中的疗效有限。本研究探索了将溶瘤腺病毒与高效铁死亡诱导剂Erastin联用，以增强溶瘤病毒不敏感癌细胞系的抗肿瘤效果。体外实验表明，与单药治疗相比，Erastin显著增强了溶瘤病毒疗法的细胞毒性，从而更有效地抑制细胞增殖并提高细胞死亡率。联合治疗进一步促进了铁死亡，其证据包括活性氧（ROS）水平升高、脂质过氧化作用增强以及氧化还原稳态失衡。RNA测序分析发现Dickkopf-1（DKK1）的下调是增强铁死亡效应的关键介质。恢复DKK1表达可部分减轻联合疗法的细胞毒性效应，凸显其在介导铁死亡增强溶瘤病毒疗效中的关键作用。体内研究进一步验证了这些发现，表明联合治疗能显著抑制肿瘤生长且未诱发明显毒性。这种新型治疗策略通过诱导铁死亡，对增强溶瘤病毒耐药性癌症的溶瘤病毒疗效具有巨大潜力。有必要在临床相关模型中进行深入研究，以全面阐明其潜在机制并优化该联合策略的临床应用前景。

原文链接：

Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer