Salidroside suppresses the metastasis of hepatocellular carcinoma cells by inhibiting the activation of the Notch1 signaling pathway

Mol Med Rep. 2019 Jun;19(6):4964-4972. doi: 10.3892/mmr.2019.10115. Epub 2019 Apr 2.

Abstract

Salidroside (SDS) is a phenylpropanoid glycoside isolated from Rhodiola rosea L. It exhibits multiple pharmacological properties in clinical medicine and has been commonly used in traditional Chinese medicine. The present study investigated the inhibitory effects of SDS on tumor invasion and migration, and the expression of metastasis‑related genes in highly metastatic hepatocellular carcinoma (HCC) cells (MHCC97H) in vitro. The underlying mechanisms of SDS on the tumor metastasis were also explored. SDS was found to significantly reduce wound closure areas and inhibit cell migration. In addition, SDS markedly inhibited the invasion of these cells into Matrigel‑coated membranes. SDS markedly downregulated the expression of Notch1, Snail, COX‑2, MMP‑2, MMP‑9 genes and upregulated the expression of E‑cadherin in a dose‑dependent manner. Furthermore, SDS inhibited the expression of the Notch signaling target genes, Hey1, Hes1 and Hes5. On the whole, the findings of this study suggest that SDS inhibits HCC cell metastasis by modulating the activity of the Notch1 signaling pathway.

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Down-Regulation / drug effects
  • Glucosides / pharmacology*
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Phenols / pharmacology*
  • Receptor, Notch1 / antagonists & inhibitors
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / drug effects*
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Transcription Factor HES-1 / genetics
  • Transcription Factor HES-1 / metabolism

Substances

  • Cadherins
  • Glucosides
  • Phenols
  • Receptor, Notch1
  • Snail Family Transcription Factors
  • Transcription Factor HES-1
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • rhodioloside