Resveratrol Inhibits Hepatocellular Carcinoma Progression through Regulating Exosome Secretion

Curr Med Chem. 2024;31(15):2107-2118. doi: 10.2174/0929867331666230914090053.

Abstract

Background and objectives: Resveratrol is a promising drug for tumor therapy, but its anti-tumor mechanism remains unclarified. The present study aimed to explore the effect of resveratrol on the secretion of exosomes and the role of resveratrol-induced exosomes in the progression of hepatocellular carcinoma.

Methods: The number and contents of exosomes induced by resveratrol were determined by nanoparticle tracking analysis and high-throughput sequencing in Huh7 cells, respectively. Expression of Rab27a was assessed by western blotting and immunofluorescence. Cell proliferation, migration and epithelial-mesenchymal transition were examined with the stimuli of resveratrol and exosomes, the activity of autophagy and wnt/β-catenin signaling induced by resveratrol-induced exosomes and knockdown of lncRNA SNHG29 were monitored by western blotting and immunofluorescence.

Results: It was found that resveratrol might inhibit the exosome secretion by down-regulating the expression of Rab27a, thereby suppressing the proliferation, migration and epithelial-mesenchymal transition of Huh7 cells. Moreover, resveratrol-induced exosomes could also inhibit the malignant phenotype of Huh7 cells via inhibiting the nuclear translocation of β-catenin and the activation of autophagy, which lncRNA SNHG29 might mediate.

Conclusion: Resveratrol inhibits hepatocellular carcinoma progression by regulating exosome secretion and contents.

Keywords: Hepatocellular carcinoma; autophagy; exosome; lncRNA; nano-particle.; resveratrol.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Resveratrol / metabolism
  • Resveratrol / pharmacology
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Resveratrol
  • RNA, Long Noncoding