Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Vitexin Inhibits Gastric Cancer Growth and Metastasis through HMGB1-mediated Inactivation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway

  • Zhou, Peng (Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University) ;
  • Zheng, Zi-Han (Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital) ;
  • Wan, Tao (Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital) ;
  • Wu, Jie (Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital) ;
  • Liao, Chuan-Wen (Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital) ;
  • Sun, Xue-Jun (Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University)
  • Received : 2021.07.21
  • Accepted : 2021.12.14
  • Published : 2021.12.31
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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.

Keywords

Acknowledgement

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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