Targeting the SMG9–Wnt/β-catenin axis: A novel mechanism by which ginsenoside Rh2 suppresses triple-negative breast cancer progression
4 affiliations
- 1Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
- 2Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China.
- 3Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
- 4Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Abstract
Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options, underscoring the need for new treatment approaches. Ginsenoside Rh2 (G-Rh2) has demonstrated antitumor effects across multiple cancer types; however, its effects and underlying molecular mechanisms in TNBC remain poorly understood. Methods: TNBC cell viability was measured using the CCK-8 assay.Flow cytometry was used to evaluate cell cycle distribution and cell apoptosis. Proteomic analysis was performed to identify potential downstream targets of G-Rh2. The functional roles of downstream targets were validated by western blotting, flow cytometry, and luciferase reporter assays. Molecular docking was conducted to characterize protein-ligand interactions at the atomic level. Results: G-Rh2 markedly decreased MDA-MB-468 and BT549 cells viability in a concentration-dependent manner, with IC50 values of 31.74 μM and 49.63 μM, respectively. G-Rh2 treatment induced G0/G1 phase arrest and enhanced cell apoptosis. Mechanistically, G-Rh2 suppressed the Wnt/β-catenin signaling pathway through SMG9 downregulation. Molecular docking demonstrated a stable interaction between G-Rh2 and SMG9, with a minimum binding energy of −3.4 kcal/mol, indicating direct molecular engagement. Conclusion: This study demonstrates that G-Rh2 exerts potent antitumor effects in TNBC by inducing cell cycle arrest and promoting cell apoptosis. Furthermore, G-Rh2 suppresses tumor progression by targeting the SMG9-Wnt/β-catenin axis. These findings identify SMG9 as a novel mediator of G-Rh2 activity, provide mechanistic insight into its antitumor effects, and highlight SMG9 as a promising therapeutic target for TNBC.
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BibTeX
@article{liu2026targeting,
title = {{Targeting the SMG9–Wnt/β-catenin axis: A novel mechanism by which ginsenoside Rh2 suppresses triple-negative breast cancer progression}},
author = {Shuang Liu and Yueqi Wang and Ye Zhang and Kun Chen and Yi-Nan Wang and Qiaoxuan Zhang and Xing Jin},
journal = {Journal of Ginseng Research},
year = {2026},
month = jul,
doi = {10.1016/j.jgr.2026.101112},
url = {https://doi.org/10.1016/j.jgr.2026.101112},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Targeting the SMG9–Wnt/β-catenin axis: A novel mechanism by which ginsenoside Rh2 suppresses triple-negative breast cancer progression
AU - Shuang Liu
AU - Yueqi Wang
AU - Ye Zhang
AU - Kun Chen
AU - Yi-Nan Wang
AU - Qiaoxuan Zhang
AU - Xing Jin
PY - 2026
DA - 2026/07/14
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101112
UR - https://doi.org/10.1016/j.jgr.2026.101112
AB - Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options, underscoring the need for new treatment approaches. Ginsenoside Rh2 (G-Rh2) has demonstrated antitumor effects across multiple cancer types; however, its effects and underlying molecular mechanisms in TNBC remain poorly understood. Methods: TNBC cell viability was measured using the CCK-8 assay.Flow cytometry was used to evaluate cell cycle distribution and cell apoptosis. Proteomic analysis was performed to identify potential downstream targets of G-Rh2. The functional roles of downstream targets were validated by western blotting, flow cytometry, and luciferase reporter assays. Molecular docking was conducted to characterize protein-ligand interactions at the atomic level. Results: G-Rh2 markedly decreased MDA-MB-468 and BT549 cells viability in a concentration-dependent manner, with IC50 values of 31.74 μM and 49.63 μM, respectively. G-Rh2 treatment induced G0/G1 phase arrest and enhanced cell apoptosis. Mechanistically, G-Rh2 suppressed the Wnt/β-catenin signaling pathway through SMG9 downregulation. Molecular docking demonstrated a stable interaction between G-Rh2 and SMG9, with a minimum binding energy of −3.4 kcal/mol, indicating direct molecular engagement. Conclusion: This study demonstrates that G-Rh2 exerts potent antitumor effects in TNBC by inducing cell cycle arrest and promoting cell apoptosis. Furthermore, G-Rh2 suppresses tumor progression by targeting the SMG9-Wnt/β-catenin axis. These findings identify SMG9 as a novel mediator of G-Rh2 activity, provide mechanistic insight into its antitumor effects, and highlight SMG9 as a promising therapeutic target for TNBC.
SN - 1226-8453
SN - 2093-4947
ER -