Resveratrol inhibits TGF-β1-induced EMT in gastric cancer cells through Hippo-YAP signaling pathway

Clin Transl Oncol. 2022 Nov;24(11):2210-2221. doi: 10.1007/s12094-022-02882-z. Epub 2022 Jul 17.

Abstract

Objective: To investigate the effects of resveratrol (RSVL) on epithelial-mesenchymal transition (EMT) and biological behaviors of gastric cancer cells.

Methods: SGC-7901 cells were treated with RSVL, followed by TGF-β1 treatment for induction of EMT. Cell proliferation was tested by MTT assay, migration and invasion by Transwell and scratch assays, and Hippo-YAP signaling pathway activation by immunofluorescence. The RNA and protein expressions of E-cadherin, Vimentin, N-cadherin, and Snail were detected by qPCR and Western blot. A tumor model was constructed to examine the effect of RSVL on gastric tumor growth.

Results: RSVL inhibited the migration, invasion, and growth of gastric cancer cells in concentration- and time-dependent manners. RSVL inhibited TGF-β1-induced EMT of gastric cancer cells, which might relate to inactivation of the Hippo-YAP pathway. In the mouse tumor model, RSVL inhibited the EMT process by suppressing the Hippo-YAP pathway.

Conclusion: RSVL inhibited EMT of gastric cancer cells probably by weakening the Hippo-YAP signaling pathway.

Keywords: Epithelial-mesenchymal transition; Hippo-YAP signaling pathway; Invasion; Migration; Proliferation; Resveratrol.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition*
  • Hippo Signaling Pathway
  • Mice
  • Protein Serine-Threonine Kinases
  • RNA
  • Resveratrol / pharmacology
  • Stomach Neoplasms* / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Vimentin / metabolism
  • YAP-Signaling Proteins

Substances

  • Cadherins
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Vimentin
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • RNA
  • Stk4 protein, mouse
  • Protein Serine-Threonine Kinases
  • Resveratrol