Mechanisms of traditional Chinese medicine interventions in the gastric ‘inflammation-to-carcinoma’ cascade: advances in in vitro models from monolayer cells to organoids
- 1Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
Abstract
Gastric cancer remains a leading cause of cancer-related mortality worldwide. The Correa cascade, progressing from chronic gastritis through precancerous lesions to adenocarcinoma, provides the framework for understanding gastric mucosal stepwise malignant transformation. Traditional Chinese Medicine (TCM) formulas, such as Zuojin Pills and Wuji Pills, have been historically used to treat gastric disorders including epigastric pain and acid regurgitation, yet their mechanisms of action in blocking the inflammation-to-carcinoma transition remain incompletely understood. The mechanistic diversity of TCM presents challenges for in vitro modeling, and existing reviews have not systematically addressed how model selection should align with specific research questions across different stages of the cascade. This review examines the evolving landscape of in vitro models used in TCM research on gastric mucosal inflammation-to-carcinoma transition, highlighting the paradigm shift from two-dimensional (2D) monolayer GES-1 cell cultures to three-dimensional gastric organoids. We analyzed recent studies conducted across multiple model platforms using various acute or chronic pathogenic factors, with all botanical drugs validated taxonomically through authoritative sources. The GES-1 cell model offers low cost, high throughput, and genetic homogeneity, making it suitable for initial screening of active metabolites from botanical drugs and for dissecting molecular pathways, particularly those involving Nrf2, NF-κB, PI3K/AKT, and MAPK signaling in antioxidative stress, anti-inflammatory, and anti-apoptotic mechanisms. In contrast, gastric organoids preserve three-dimensional architecture, cellular diversity, and patient-specific genetic backgrounds, enabling functional assessment of barrier integrity, stem cell-driven regeneration, and malignant transformation at the tissue level. To address the need for evidence differentiation, we introduce a hierarchical framework (Model Evidence Level) in which GES-1 cells serve for entry-level target discovery and patient-derived organoids for higher-level tissue validation. Based on this framework, we provide stage-specific model selection recommendations corresponding to the distinct phases of the Correa cascade: acute inflammation, chronic atrophy, intestinal metaplasia, dysplasia, and gastric cancer. This review offers a practical, evidence-stratified pathway for in vitro model selection in TCM intervention studies, bridging traditional ethnopharmacological knowledge with modern pharmacological validation to strengthen the translational relevance of preclinical findings.
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BibTeX
@article{zhang2026mechanisms,
title = {{Mechanisms of traditional Chinese medicine interventions in the gastric ‘inflammation-to-carcinoma’ cascade: advances in in vitro models from monolayer cells to organoids}},
author = {Xiaoling Zhang and Tiangang Wang and Xusen Zeng and Xin Zhou and Long Zhao},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1906847},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1906847/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanisms of traditional Chinese medicine interventions in the gastric ‘inflammation-to-carcinoma’ cascade: advances in in vitro models from monolayer cells to organoids
AU - Xiaoling Zhang
AU - Tiangang Wang
AU - Xusen Zeng
AU - Xin Zhou
AU - Long Zhao
PY - 2026
DA - 2026/10/13
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1906847
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1906847/full
AB - Gastric cancer remains a leading cause of cancer-related mortality worldwide. The Correa cascade, progressing from chronic gastritis through precancerous lesions to adenocarcinoma, provides the framework for understanding gastric mucosal stepwise malignant transformation. Traditional Chinese Medicine (TCM) formulas, such as Zuojin Pills and Wuji Pills, have been historically used to treat gastric disorders including epigastric pain and acid regurgitation, yet their mechanisms of action in blocking the inflammation-to-carcinoma transition remain incompletely understood. The mechanistic diversity of TCM presents challenges for in vitro modeling, and existing reviews have not systematically addressed how model selection should align with specific research questions across different stages of the cascade. This review examines the evolving landscape of in vitro models used in TCM research on gastric mucosal inflammation-to-carcinoma transition, highlighting the paradigm shift from two-dimensional (2D) monolayer GES-1 cell cultures to three-dimensional gastric organoids. We analyzed recent studies conducted across multiple model platforms using various acute or chronic pathogenic factors, with all botanical drugs validated taxonomically through authoritative sources. The GES-1 cell model offers low cost, high throughput, and genetic homogeneity, making it suitable for initial screening of active metabolites from botanical drugs and for dissecting molecular pathways, particularly those involving Nrf2, NF-κB, PI3K/AKT, and MAPK signaling in antioxidative stress, anti-inflammatory, and anti-apoptotic mechanisms. In contrast, gastric organoids preserve three-dimensional architecture, cellular diversity, and patient-specific genetic backgrounds, enabling functional assessment of barrier integrity, stem cell-driven regeneration, and malignant transformation at the tissue level. To address the need for evidence differentiation, we introduce a hierarchical framework (Model Evidence Level) in which GES-1 cells serve for entry-level target discovery and patient-derived organoids for higher-level tissue validation. Based on this framework, we provide stage-specific model selection recommendations corresponding to the distinct phases of the Correa cascade: acute inflammation, chronic atrophy, intestinal metaplasia, dysplasia, and gastric cancer. This review offers a practical, evidence-stratified pathway for in vitro model selection in TCM intervention studies, bridging traditional ethnopharmacological knowledge with modern pharmacological validation to strengthen the translational relevance of preclinical findings.
SN - 1663-9812
ER -