Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway

Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have repor...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-07, Vol.25 (14), p.7973
Main Authors: Wei, Xin, Liu, Qunshan, Liu, Liu, Wang, Dan, Liu, Jiajia, Zhu, Qizhi, Xu, Ziming, Chen, Qi, Xu, Weiping
Format: Article
Language:English
Subjects:
5-FU
Apoptosis
Cancer therapies
Cell cycle
Chemotherapy
epithelial to mesenchymal transition
Erianin
Gastric cancer
Gene expression
Kinases
LKB1
Lung cancer
Medical prognosis
Metastasis
Mortality
Mutation
Ovarian cancer
PARD3
Patients
Proteins
Surgery
Tumors
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Summary:Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients' tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial-mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25147973