Schisandrin B Suppresses Pancreatic Ductal Adenocarcinoma Through EGFR/AKT/mTOR Signaling and Mitochondrial Dysfunction
- 1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
- 2Department of Convergent Biotechnology and Advanced Materials Science, College of Life Sciences, Kyung Hee University, Yongin 17104, Republic of Korea
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with poor prognosis due to chemoresistance and limited treatment options. Schisandrin B (Sch B), a bioactive compound from Schisandra chinensis, has demonstrated anticancer effects in various malignancies, but its role in PDAC remains unknown. This study explores the antitumor mechanisms of Sch B using network pharmacology, molecular docking, and in vitro and in vivo experiments, focusing on the EGFR/AKT/mTOR signaling pathway and mitochondrial dysfunction. Network pharmacology identified EGFR, CASP3, BCL2, and HSP90 as key candidate targets of Sch B, and molecular docking and MD simulation were used to explore putative interactions with these proteins. In PDAC cells, treatment Sch B for 48 h reduced cell viability. In addition, Sch B suppressed EGFR/AKT/mTOR signaling and induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, increased mitochondrial and cytosolic calcium levels, and elevated ROS production, accompanied by activation of apoptotic signaling. Co-treatment with gemcitabine demonstrated enhanced effects, elevating apoptosis and oxidative stress. Moreover, Sch B significantly reduced tumor growth in a PANC-1 xenograft model, accompanied by decreased protein expression of EGFR, AKT, mTOR, and HSP90 in tumor tissues. These findings suggest that Sch B exerts antitumor activity associated with modulation of EGFR/AKT/mTOR signaling and mitochondrial dysfunction, supporting further investigation of Sch B as a potential therapeutic candidate for PDAC, particularly in combination with standard chemotherapy.
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BibTeX
@article{lee2026schisandrin,
title = {{Schisandrin B Suppresses Pancreatic Ductal Adenocarcinoma Through EGFR/AKT/mTOR Signaling and Mitochondrial Dysfunction}},
author = {Woonghee Lee and Gwonhwa Song and Hyocheol Bae},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219996},
url = {https://www.mdpi.com/1422-0067/27/21/9996},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Schisandrin B Suppresses Pancreatic Ductal Adenocarcinoma Through EGFR/AKT/mTOR Signaling and Mitochondrial Dysfunction
AU - Woonghee Lee
AU - Gwonhwa Song
AU - Hyocheol Bae
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219996
UR - https://www.mdpi.com/1422-0067/27/21/9996
AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with poor prognosis due to chemoresistance and limited treatment options. Schisandrin B (Sch B), a bioactive compound from Schisandra chinensis, has demonstrated anticancer effects in various malignancies, but its role in PDAC remains unknown. This study explores the antitumor mechanisms of Sch B using network pharmacology, molecular docking, and in vitro and in vivo experiments, focusing on the EGFR/AKT/mTOR signaling pathway and mitochondrial dysfunction. Network pharmacology identified EGFR, CASP3, BCL2, and HSP90 as key candidate targets of Sch B, and molecular docking and MD simulation were used to explore putative interactions with these proteins. In PDAC cells, treatment Sch B for 48 h reduced cell viability. In addition, Sch B suppressed EGFR/AKT/mTOR signaling and induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, increased mitochondrial and cytosolic calcium levels, and elevated ROS production, accompanied by activation of apoptotic signaling. Co-treatment with gemcitabine demonstrated enhanced effects, elevating apoptosis and oxidative stress. Moreover, Sch B significantly reduced tumor growth in a PANC-1 xenograft model, accompanied by decreased protein expression of EGFR, AKT, mTOR, and HSP90 in tumor tissues. These findings suggest that Sch B exerts antitumor activity associated with modulation of EGFR/AKT/mTOR signaling and mitochondrial dysfunction, supporting further investigation of Sch B as a potential therapeutic candidate for PDAC, particularly in combination with standard chemotherapy.
SN - 1422-0067
ER -