Cytotoxic effect of bladder cancer oncolytic virus on bladder cancer stem-like cells via pyroptosis pathway.

IF 1.8 4区医学 Q4 ENGINEERING, BIOMEDICAL

Technology and Health Care Pub Date : 2025-09-01 Epub Date: 2025-06-11 DOI:10.1177/09287329251349081

Xin Cao, Dongyang Gao, Su Zhang, Xiaoquan Yu, Xin Su, Jianzhong Lu, Zhiping Wang

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引用次数: 0

Abstract

Background: The main treatment plan for bladder cancer is surgery combined with postoperative chemotherapy. Patients often suffer from various adverse reactions after chemotherapy, which reduces the quality of life. Moreover, after chemotherapy, the resistance to chemotherapy drugs of tumor is often increased, and the tumor resistance to chemotherapy drugs is often accompanied by the deterioration of pathological classification, distant metastasis, and the decline of patients' survival period. Recent studies have found that cancer stem cells play a crucial role in tumor proliferation, invasion, metastasis and drug resistance.

Objective: This study would prove oncolytic adenovirus Ad5-E1A-UPII-PSCAE emerges as a potent agent against bladder cancer stem-like cells (CSCs), and triggers reactive oxygen species (ROS) accumulation, culminating in pyroptosis.

Methods: This study is based on transcriptome and proteomic analysis, supplemented by in vivo and in vitro experiments for validation.

Result: In vitro studies confirmed dose-dependent CSC killing (IC50: 3.6 × 10⁹ PFU), while transcriptomic and proteomic analyses highlighted mitochondrial dysfunction and ROS-driven pathways as central mechanisms. In vivo, OV-treated xenografts exhibited significant tumor regression and histopathological necrosis. By exploiting the NO/ROS-pyroptosis axis, Ad5-E1A-UPII-PSCAE overcomes CSC-mediated chemoresistance, offering a dual strategy to eradicate aggressive tumor subpopulations and suppress recurrence.

Conclusion: This study results demonstrated that OVs could kill cancer stem-like cells by promoting ROS levels, which induce cell pyroptosis.

查看原文本刊更多论文

膀胱癌溶瘤病毒通过焦亡途径对膀胱癌干细胞的细胞毒作用。

背景：膀胱癌的主要治疗方案是手术加术后化疗。化疗后患者常出现各种不良反应，降低生活质量。而且，化疗后肿瘤对化疗药物的耐药性往往增加，肿瘤对化疗药物的耐药性往往伴随着病理分型的恶化、远处转移、患者生存期的下降。近年来的研究发现，肿瘤干细胞在肿瘤的增殖、侵袭、转移和耐药过程中起着至关重要的作用。目的：本研究旨在证明溶瘤腺病毒Ad5-E1A-UPII-PSCAE是一种有效的抗膀胱癌干细胞（CSCs）的药物，并引发活性氧（ROS）的积累，最终导致焦亡。方法：本研究以转录组学和蛋白质组学分析为基础，辅以体内和体外实验进行验证。结果：体外研究证实了剂量依赖性CSC杀伤（IC50: 3.6 × 109 PFU），而转录组学和蛋白质组学分析强调了线粒体功能障碍和ros驱动途径是主要机制。在体内，ov处理的异种移植物表现出明显的肿瘤消退和组织病理学坏死。通过利用NO/ ros -焦亡轴，Ad5-E1A-UPII-PSCAE克服了csc介导的化疗耐药，提供了根除侵袭性肿瘤亚群和抑制复发的双重策略。结论：本研究结果表明，OVs可通过提高ROS水平杀死肿瘤干细胞样细胞，导致细胞焦亡。

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

Technology and Health Care HEALTH CARE SCIENCES & SERVICES-ENGINEERING, BIOMEDICAL

CiteScore

2.10

自引率

6.20%

发文量

282

审稿时长

>12 weeks

期刊介绍： Technology and Health Care is intended to serve as a forum for the presentation of original articles and technical notes, observing rigorous scientific standards. Furthermore, upon invitation, reviews, tutorials, discussion papers and minisymposia are featured. The main focus of THC is related to the overlapping areas of engineering and medicine. The following types of contributions are considered: 1.Original articles: New concepts, procedures and devices associated with the use of technology in medical research and clinical practice are presented to a readership with a widespread background in engineering and/or medicine. In particular, the clinical benefit deriving from the application of engineering methods and devices in clinical medicine should be demonstrated. Typically, full length original contributions have a length of 4000 words, thereby taking duly into account figures and tables. 2.Technical Notes and Short Communications: Technical Notes relate to novel technical developments with relevance for clinical medicine. In Short Communications, clinical applications are shortly described. 3.Both Technical Notes and Short Communications typically have a length of 1500 words. Reviews and Tutorials (upon invitation only): Tutorial and educational articles for persons with a primarily medical background on principles of engineering with particular significance for biomedical applications and vice versa are presented. The Editorial Board is responsible for the selection of topics. 4.Minisymposia (upon invitation only): Under the leadership of a Special Editor, controversial or important issues relating to health care are highlighted and discussed by various authors. 5.Letters to the Editors: Discussions or short statements (not indexed).