J Gastric Cancer.  2021 Dec;21(4):439-456. 10.5230/jgc.2021.21.e40.

Vitexin Inhibits Gastric Cancer Growth and Metastasis through HMGB1-mediated Inactivation of the PI3K/ AKT/mTOR/HIF-1α Signaling Pathway

Affiliations
  • 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People's Republic of China
  • 2Department of Gastrointestinal Surgery, Jiangxi Provincial People’s Hospital, Nanchang, People's Republic of China

Abstract

Purpose
Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism.
Materials and Methods
The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry.
Results
Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression.
Conclusions
Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

Keyword

Epithelial-Mesenchymal transition; Gastric cancer; Hypoxia; Phosphatidylinositols; Vitexin
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