Molecular mechanism of raddeanin A in anti-nasopharyngeal carcinoma mediated by ERK/MAPK signaling pathway
10.13200/j.cnki.cjb.004453
- VernacularTitle:ERK/MAPK信号通路介导银莲花素A抗鼻咽癌的分子机制
- Author:
Jiajie CHEN
1
Author Information
1. School of Basic Medicine, Chengdu Medical College, Chengdu 610500, Sichuan Province, China Corresponding authors: YANG Ping, E⁃mail: yangping@cmc.edu.cn;
- Publication Type:Journal Article
- Keywords:
Raddeanin A(RA);
Nasopharyngeal carcinoma(NPC);
Network pharmacology;
Molecular docking;
Apoptosis;
ERK/MAPK signaling pathway
- From:
Chinese Journal of Biologicals
2026;39(02):152-161
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the biological activity of raddeanin A(RA) against nasopharyngeal carcinoma(NPC)and the molecular mechanism of anti-NPC mediated by ERK/MAPK signaling pathway.Methods CCK-8 assay was used to detect the inhibitory effect of RA on the growth of NPC cells. Bioinformatics was utilized to predict the targets of RA acting on NPC and their associated signaling pathways. The binding affinity between RA and core target was analyzed by molecular docking. Annexin V-FITC/PI, JC-1 staining, flow cytometry, combined with Western blot were used to further investigate the anti-proliferation mechanism of RA in NPC cells.Results RA effectively inhibited the proliferation of NPC cell lines 6-10B and 5-8F, with IC_(50)values of 5. 770 and 5. 068 ??mol/L, respectively. The pharmacological effects were primarily associated with cell apoptosis and the MAPK signaling pathway. The binding affinities between RA and core target proteins, such as MAPK1 and caspase 3, predicted through molecular docking, were less than-5 kcal/mol. RA induced apoptosis and mitochondrial membrane potential changes in 6-10B cells. The expression levels of apoptosis-related proteins, including cleaved PARP, cleaved caspase 3, and cleaved caspase 9, significantly increased(F = 229. 60, 136. 60 and 73. 67, P < 0. 001,< 0. 001 and < 0. 01, respectively). Additionally, the expression of the mitochondrial pathway-related protein Bax was marked-ly upregulated, while Bcl-2 expression was significantly downregulated(F = 47. 42 and 17. 54, P < 0. 001 and P < 0. 05,respectively). Furthermore, the expression levels of ERK/MAPK pathway-related proteins, including p-p90 RSK, p-ERK1/2,and p-MSK1, were significantly reduced(F = 106. 90, 27. 73 and 101. 50, P < 0. 05, < 0. 01 and < 0. 05, respectively).Conclusion RA regulates the ERK/MAPK signaling pathway, reduces mitochondrial membrane potential, triggers mitochondrial pathway to induce apoptosis, and then exerts the activity of inhibiting NPC cell proliferation.
