Apatinib inhibits the proliferation of gastric cancer cells via the AKT/GSK signaling pathway in vivo

Aging (Albany NY). 2021 Aug 27;13(16):20738-20747. doi: 10.18632/aging.203458. Epub 2021 Aug 27.

Abstract

Gastric cancer (GC) is the third leading cause of cancer-associated mortality globally. Although the diagnosis and therapeutic strategies for GC have improved, the prognosis for advanced gastric cancer (AGC) remains poor. Hence, the present study sought to design a zebrafish model established by microinjecting human MGC-803 GC cell line for studying personalized molecular-targeted cancer therapy. Apatinib, a novel molecular-targeted agent, was evaluated for its in vivo efficacy through a comparison among the control groups (no treatment) and subject groups (treatment). Newly formed vessel length and tumor volume were measured in all of the groups for further study. The length of newly formed vessels was obviously shortened after apatinib treatment in the zebrafish model established in this study. Meanwhile, apatinib exhibited the best antitumor growth effect with dose and time dependence by suppressing AKT/GSK3α/β signaling, which may be the mechanism underlying the profound antitumor clinical effect of apatinib. The data indicated that apatinib therapy exerts an anti-angiogenesis effect and it can be recommended as a proper antitumor growth therapy for GC patients. Additionally, zebrafish models could be designed as a potential practical tool to explore new anti-GC cancer drugs.

Keywords: AKT/GSK signaling; angiogenesis; apatinib; gastric cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Disease Models, Animal
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Humans
  • Molecular Targeted Therapy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyridines / administration & dosage*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / physiopathology
  • Xenograft Model Antitumor Assays
  • Zebrafish

Substances

  • Antineoplastic Agents
  • Pyridines
  • apatinib
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3