Tetrandrine inhibits migration and invasion of BGC-823 and MKN-45 cells by regulating PI3K/AKT/mTOR signaling pathway

Chem Biol Drug Des. 2023 Apr;101(4):927-936. doi: 10.1111/cbdd.14202. Epub 2023 Jan 19.

Abstract

Tetrandrine (Tet), a traditional Chinese herbal medicine extract, exhibits anti-cancer effect on many types of cancer. Nonetheless, the action mechanism of Tet in gastric cancer (GC) is still largely unclear. In the current study, proliferation, invasion, and migration of the BGC-823 and MKN-45 cells were effectively suppressed by Tet treatment in a dose-dependent manner. Moreover, Tet suppressed expression of the proliferation-associated protein PCNA, the interstitial cell phenotype N-cadherin, and the extracellular matrix-associated MMP-2 and MMP-9 in BGC-823 and MKN-45 cells in a dose-dependent manner. PI3K/AKT/mTOR, a cancer promoting signaling, was inactivated by Tet in a dose-dependent manner in BGC-823 and MKN-45 cells. Furthermore, our results demonstrated that the inhibition of Tet to PCNA, N-cadherin, MMP-2, and MMP-9 expression was partly rescuedby AKT inhibitor or mTOR inhibitor. In animal experiments, tumor growth was inhibited by Tet administration in a dose-dependent manner. In conclusion, the current data indicated that Tet had a critical effect on inhibiting BGC-823 and MKN-45 cells proliferation, migration, invasion, and tumor growth via regulating PI3K/AKT/mTOR signaling pathway, suggesting that Tet might be a potential treatment for GC.

Keywords: anti-tumor; gastric cancer; natural product; tetrandrine; traditional Chinese medicine.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proliferating Cell Nuclear Antigen / pharmacology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Stomach Neoplasms*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • tetrandrine
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 2
  • Phosphatidylinositol 3-Kinases
  • Proliferating Cell Nuclear Antigen
  • TOR Serine-Threonine Kinases