A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways

Int J Biol Macromol. 2019 May 15:129:706-714. doi: 10.1016/j.ijbiomac.2019.02.040. Epub 2019 Feb 7.

Abstract

In this study we investigated the potential effects of a polysaccharide (HDP) from Hedyotis diffusa on the metastasis in human lung adenocarcinoma A549 cells. HDP (25, 50 and 100μg/ml) significantly suppressed the cell adhesion, invasion and migration of A549 cells in a dose dependent manner by downregulation of matrix metalloproteinase (MMP-2 and MMP-9) and upregulation of tissue inhibitors of metalloproteinase (TIMP-2 and TIMP-9). Moreover, HDP effectively downregulated the protein expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin), and upregulated E-cadherin protein expression, which is involved in interrupting EGFR/Akt/ERK signaling pathways, as well as inhibiting COX-2 protein expression. All these results demonstrated that HDP might be a novel anti-metastatic agent for NSCLC treatment.

Keywords: Hedyotis diffusa polysaccharide; Lung adenocarcinoma A549 cells; Metastasis.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / pathology*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cyclooxygenase 2 / metabolism
  • Enzyme Activation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hedyotis / chemistry*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*

Substances

  • Polysaccharides
  • Cyclooxygenase 2
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9