Agrimoniin combines with erlotinib to inhibit the proliferation of pancreatic cancer cells by suppressing signal interactions in the tumor microenvironment and disrupting two positive feedback loops involving lactic acid production.
12 affiliations
- 1School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
- 2Key Laboratory of Drug Target and Drug for Degenerative Disease, School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, Jiangsu, China.
- 3Ili & Jiangsu Joint Institute of Health, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Yining, China.
- 4Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
- 5College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
- 6School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
- 7School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
- 8Singleron Biotechnologies, Nanjing, China.
- 9Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. [email protected].
- 10Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. [email protected].
- 11School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China. [email protected].
- 12Key Laboratory of Drug Target and Drug for Degenerative Disease, School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, Jiangsu, China. [email protected].
Abstract
Background
Erlotinib, an epidermal growth factor receptor (EGFR) small molecule inhibitor approved by the Food and Drug Administration (FDA) for the treatment of pancreatic cancer, faces significant drug resistance challenges. To address this, we investigated the potential of agrimoniin, a key active compound in the traditional Chinese medicine Agrimonia pilosa, which is known for its potent anticancer activity. This study aims to explore the combined effect of these two compounds in pancreatic cancer.Methods
We sought to verify the combined inhibitory effect of pancreatic cancer by agrimoniin and erlotinib in vitro and in vivo using various assays, including subcutaneous xenograft experiments and western blot. Single-cell RNA sequencing, bioinformatics, western blot, and lactic acid assays were performed to study how agrimoniin and erlotinib affect the tumor microenvironment and aerobic glycolysis. Finally, using signal pathway inhibitors/agonists, lactic acid assays, and Western blot, we aimed to reveal two positive feedback loops between signal pathways and lactic acid production.Results
Agrimoniin combines with erlotinib to inhibit proliferation of pancreatic cancer cells. Together, they effectively suppress signal interactions between tumor cells, stromal cells, and macrophages within subcutaneous tumors. Simultaneously, they jointly inhibit aerobic glycolysis and lactic acid production in pancreatic cancer. Notably, this study proposes two potentially novel positive feedback loops between the PI3K/AKT/HIF-1α/HK2, MEK/ERK/HIF-1α/HK2 signaling pathways and lactic acid production.Conclusions
The combination of agrimoniin and erlotinib suppresses signal interactions between tumor cells, macrophages, and stromal cells in the tumor microenvironment, reprograms aerobic glycolysis, disrupts two positive feedback loops, thereby cooperatively inhibiting the proliferation of pancreatic cancer cells. This study provides a theoretical basis for agrimoniin as a sensitizer or resistance-reversing agent for erlotinib, and offers new insights and potential targets for pancreatic cancer drug development.
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BibTeX
@article{zhang2026agrimoniin,
title = {{Agrimoniin combines with erlotinib to inhibit the proliferation of pancreatic cancer cells by suppressing signal interactions in the tumor microenvironment and disrupting two positive feedback loops involving lactic acid production.}},
author = {Xiongfei Zhang and Xinyi Xia and Yan Wang and Huanhuan Zhao and Huiying Xu and Yutong Liu and Lei Li and Shaojun Wang and Qinlong Dai and Ling Gu and Yiwen Chen and Xinye Dong and Beili Xi and Li Tao and Yang Hua and Zhihan Zhang and Xinyue Tian and Yuyan Ling and Tingting Xu and Yi Zhu and Jingjing Zhang and Lifeng Zhu},
journal = {Cellular \& molecular biology letters},
year = {2026},
month = aug,
doi = {10.1186/s11658-026-01000-z},
url = {https://europepmc.org/article/MED/43009796},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Agrimoniin combines with erlotinib to inhibit the proliferation of pancreatic cancer cells by suppressing signal interactions in the tumor microenvironment and disrupting two positive feedback loops involving lactic acid production.
AU - Xiongfei Zhang
AU - Xinyi Xia
AU - Yan Wang
AU - Huanhuan Zhao
AU - Huiying Xu
AU - Yutong Liu
AU - Lei Li
AU - Shaojun Wang
AU - Qinlong Dai
AU - Ling Gu
AU - Yiwen Chen
AU - Xinye Dong
AU - Beili Xi
AU - Li Tao
AU - Yang Hua
AU - Zhihan Zhang
AU - Xinyue Tian
AU - Yuyan Ling
AU - Tingting Xu
AU - Yi Zhu
AU - Jingjing Zhang
AU - Lifeng Zhu
PY - 2026
DA - 2026/08/10
JO - Cellular & molecular biology letters
DO - 10.1186/s11658-026-01000-z
UR - https://europepmc.org/article/MED/43009796
AB - Background Erlotinib, an epidermal growth factor receptor (EGFR) small molecule inhibitor approved by the Food and Drug Administration (FDA) for the treatment of pancreatic cancer, faces significant drug resistance challenges. To address this, we investigated the potential of agrimoniin, a key active compound in the traditional Chinese medicine Agrimonia pilosa, which is known for its potent anticancer activity. This study aims to explore the combined effect of these two compounds in pancreatic cancer.Methods We sought to verify the combined inhibitory effect of pancreatic cancer by agrimoniin and erlotinib in vitro and in vivo using various assays, including subcutaneous xenograft experiments and western blot. Single-cell RNA sequencing, bioinformatics, western blot, and lactic acid assays were performed to study how agrimoniin and erlotinib affect the tumor microenvironment and aerobic glycolysis. Finally, using signal pathway inhibitors/agonists, lactic acid assays, and Western blot, we aimed to reveal two positive feedback loops between signal pathways and lactic acid production.Results Agrimoniin combines with erlotinib to inhibit proliferation of pancreatic cancer cells. Together, they effectively suppress signal interactions between tumor cells, stromal cells, and macrophages within subcutaneous tumors. Simultaneously, they jointly inhibit aerobic glycolysis and lactic acid production in pancreatic cancer. Notably, this study proposes two potentially novel positive feedback loops between the PI3K/AKT/HIF-1α/HK2, MEK/ERK/HIF-1α/HK2 signaling pathways and lactic acid production.Conclusions The combination of agrimoniin and erlotinib suppresses signal interactions between tumor cells, macrophages, and stromal cells in the tumor microenvironment, reprograms aerobic glycolysis, disrupts two positive feedback loops, thereby cooperatively inhibiting the proliferation of pancreatic cancer cells. This study provides a theoretical basis for agrimoniin as a sensitizer or resistance-reversing agent for erlotinib, and offers new insights and potential targets for pancreatic cancer drug development.
SN - 1425-8153
SN - 1689-1392
ER -