Ginsenoside Rh4 Suppresses Notch3 and PI3K/Akt Pathway to Inhibit Growth and Metastasis of Gastric Cancer Cells
DOI:
https://doi.org/10.62382/jcbt.v2i1.51Keywords:
Gastric cancer, Ginsenoside Rh4, Notch3, PI3K/Akt pathwayAbstract
Background: Rh4 (a compound derived from ginsenoside) has excellent anti-tumor property. It has been documented that an abnormally elevated level of Notch3 expression is linked to poor prognosis of gastric cancer (GC). Currently, the function of Rh4 in GC malignant progression is still unclear, and the manner in which Notch3 regulates GC progression remains undefined.
Methods: The level of Notch3 in GC cells was determined utilizing qRT-PCR and western blot. The relationship between Notch3 level and patient overall survival was forecasted by Kaplan-Meier Plotter database. The impacts of Notch3 and Rh4 on the biological characteristics of GC cells were examined through CCK-8, clone formation, scratch healing, and transwell assay. Using western blot, PI3K/Akt pathway protein levels were measured. Finally, a mouse subcutaneous transplantation tumor model was utilized to explore the influence of Rh4 treatment in vivo.
Results: The level of Notch3 was notably elevated in GC. The patient’s overall survival exhibiting high Notch3 levels was considerably lower than those with low expression. Silencing of Notch3 reduced GC cell viability and inhibited malignant progression. Rh4 exhibited a dose-dependent decrease in GC cell viability. In addition, Rh4 significantly suppressed Notch3 levels in GC cells, with over-expression of Notch3 attenuating the inhibitory influence of Rh4 on GC malignancy. Notch3 over-expression activated the PI3K/Akt pathway, while Rh4 effectively blocked this pathway by targeting Notch3, but PI3K agonists reversed this effect. Rh4 treatment reduced Notch3 expression and hindered tumor growth in vivo by inhibiting the PI3K/Akt pathway.
Conclusion: Notch3 expression was found to be heightened in GC, but Rh4 effectively suppressed PI3K/Akt pathway by targeting Notch3, and subsequently inhibiting cell proliferation, migration, and invasion.
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