Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition

Aging (Albany NY). 2020 May 20;12(10):9714-9725. doi: 10.18632/aging.103238. Epub 2020 May 20.

Abstract

Qigesan (QGS) has been used to effectively treat esophageal cancer (EC) for decades in China, but the mechanism by which it suppresses EC metastasis remains unknown. In this study, we examined the effects of QGS on EC cell mobility. Using immunohistochemistry and immunofluorescence, expression of Gas6 and Axl, which promote tumor cell migration and invasion, was examined in carcinoma tissues and adjacent normal tissues from EC patients. Levels of Gas6, Axl, and the Gas6/Axl complex were also examined in ECA109 and TE13 EC cells treated with QGS. In addition, immunofluorescent staining and quantitative protein analysis were used to examine E-cadherin, N-cadherin, and Snail levels in ECA109 and TE13 EC cells after QSG administration, and cell mobility was assessed. The results demonstrated that levels of Gas6 and Axl expression are higher in EC tissues than in adjacent normal tissues. Moreover, QGS decreased Gas6/Axl levels, increased E-cadherin expression, decreased Snail and N-cadherin expression, and inhibited epithelial-mesenchymal transition (EMT) in EC cells. QGS thus suppresses EMT in EC by inhibiting Gas6/Axl binding.

Keywords: ESCC; Gas6/Axl; TCM formulas; cancer metastasis; epithelial-mesenchymal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Axl Receptor Tyrosine Kinase
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Drugs, Chinese Herbal / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Esophageal Neoplasms / drug therapy*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • qigesan
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human