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N-甲基-N'-硝基-N-亚硝基胍在动物肿瘤模型中的作用机制与应用:现状与挑战

Mechanisms and applications of N-Methyl-N'-nitro-N-nitrosoguanidine in animal tumor models: current situation and challenges.

作者信息

Zhang Xiyan, Xu Yupei, Cao Junwen, Li Tong, Wang Jiaqi, Tao Jingna, Zhang Liju, Li Zhihong

机构信息

Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Front Oncol. 2025 Oct 23;15:1681270. doi: 10.3389/fonc.2025.1681270. eCollection 2025.

DOI:10.3389/fonc.2025.1681270
PMID:41211438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12588843/
Abstract

The worldwide health and economic burden of cancer is substantial, necessitating urgent, focused prevention and treatment strategies. The investigation of cancer animal modeling techniques is particularly critical. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a nitrosamine carcinogen, is extensively utilized in the development of several tumor animal models due to its ability to replicate the natural onset of cancer. Nonetheless, MNNG exhibits a propensity for multi-organ carcinogenesis; yet, this aspect remains undiscussed. The MNNG model exhibits distinct characteristics depending on the route of administration, yet it also presents inherent limitations such as toxicity, environmental contamination, and inconsistent modeling outcomes. These issues necessitate standardized protocols to refine the model, ensuring it meets the criteria for efficient and precise tumor induction while adhering to animal welfare principles. This study examines the current applications of MNNG in gastric cancer models and models of other organs, its carcinogenic mechanisms, translational relevance to human tumors, and practical application features, with a particular focus on its use in gastric contexts. Furthermore, it summarizes and compares the advantages and disadvantages of various MNNG administration routes, as well as contrasts its carcinogenic properties with those of other chemical inducers.Through the examination of drug administration routes, dosage effects, combined modeling strategies, and model specificity, we endeavored to identify effective methods to enhance the specificity of target organs by optimizing the administration approach (local exposure, integration of advanced detection technologies with auxiliary factors). Furthermore, we encourage researchers to disclose negative results, as this practice helps improve model stability and accuracy, reduces research costs, and aligns with animal welfare guidelines.Experimental animals are crucial in scientific study. Future investigations must develop standardized protocols to minimize non-target organ damage and examine the interaction mechanisms between these animals and the tumor microenvironment.

摘要

癌症给全球带来了巨大的健康和经济负担,因此迫切需要针对性强的预防和治疗策略。对癌症动物建模技术的研究尤为关键。N-甲基-N'-硝基-N-亚硝基胍(MNNG)是一种亚硝胺类致癌物,由于其能够模拟癌症的自然发病过程,因而被广泛应用于多种肿瘤动物模型的构建。然而,MNNG具有多器官致癌的倾向,但这一方面仍未得到充分讨论。MNNG模型根据给药途径呈现出不同的特征,但也存在诸如毒性、环境污染和建模结果不一致等固有局限性。这些问题需要标准化方案来优化该模型,以确保其在符合动物福利原则的同时,满足高效精确诱导肿瘤的标准。本研究考察了MNNG在胃癌模型及其他器官模型中的当前应用、其致癌机制、与人类肿瘤的转化相关性及实际应用特点,尤其关注其在胃部环境中的应用。此外,总结并比较了MNNG不同给药途径的优缺点,并将其致癌特性与其他化学诱导剂进行了对比。通过研究给药途径、剂量效应、联合建模策略及模型特异性,我们致力于通过优化给药方式(局部暴露、将先进检测技术与辅助因素相结合)来确定提高靶器官特异性的有效方法。此外,我们鼓励研究人员公布阴性结果,因为这种做法有助于提高模型的稳定性和准确性,降低研究成本,并符合动物福利准则。实验动物在科学研究中至关重要。未来的研究必须制定标准化方案,以尽量减少对非靶器官的损害,并研究这些动物与肿瘤微环境之间的相互作用机制。

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Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation.左金丸通过调节MEK/ERK/c-Myc信号通路减轻胃癌癌前病变:网络药理学、分子动力学模拟与实验验证的综合方法
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MiR-101-3p Promotes Tumor Cell Proliferation and Migration via the Wnt Signal Pathway in MNNG-Induced Esophageal Squamous Cell Carcinoma.MiR-101-3p通过Wnt信号通路促进MNNG诱导的食管鳞状细胞癌中的肿瘤细胞增殖和迁移。
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