Salvianolic acid A suppresses MMP-2 expression and restrains cancer cell invasion through ERK signaling in human nasopharyngeal carcinoma

J Ethnopharmacol. 2020 Apr 24:252:112601. doi: 10.1016/j.jep.2020.112601. Epub 2020 Jan 22.

Abstract

Ethnopharmacological relevance: Salvia miltiorrhiza Bunge, as known as Danshen, has used for the prevention and treatment of cardiovascular diseases clinically and anti-cancer activities. Salvianolic acid A (SAA), one of the most abundant ingredients, hydrophilic derivatives of Salvia miltiorrhiza Bunge, exerts a variety of pharmacological actions, such as anti-oxidative, anti-inflammatory and anti-cancer activities. However, the impact of SAA on nasopharyngeal carcinoma (NPC) invasion and metastasis remains unexplored.

Aim of the study: To investigate the potential of SAA to prevent migration and invasion on NPC cell.

Materials and methods: MTT assay and Boyden chamber assay were performed to determine cell proliferation, migration and invasion abilities, respectively. The activity and protein expression of matrix metalloproteinase-2 (MMP-2) were determined by gelatin zymography and western blotting.

Results: Here, we showed that SAA considerably suppressed the migrative and invasive activity of human NPC cells but not rendered cytotoxicity. In SAA-treated NPC cells, the activity and expression of matrix metalloproteinase-2 (MMP-2), a key regulator of cancer cell invasion, were reduced. Additionally, the presence of high concentrations of SAA dramatically abolished the activation of focal adhesion kinase (FAK) and moderately inhibited the phosphorylation of Src and ERK in NPC cells.

Conclusions: Our results demonstrated that SAA inhibited the migration and invasion of NPC cells, accompanied by downregulation of MMP-2 and inactivation of FAK, Src, and ERK pathways. These findings indicate a usefulness of SAA on restraining NPC invasion and metastasis.

Keywords: Invasion; MMP-2; Migration; Nasopharyngeal carcinoma; Salvianolic acid A.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Caffeic Acids / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Humans
  • Lactates / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / metabolism
  • Neoplasm Invasiveness

Substances

  • Antineoplastic Agents
  • Caffeic Acids
  • Lactates
  • Matrix Metalloproteinase Inhibitors
  • salvianolic acid A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2