Ginsenoside Rg3 Inhibition of Thyroid Cancer Metastasis Is Associated with Alternation of Actin Skeleton

J Med Food. 2018 Sep;21(9):849-857. doi: 10.1089/jmf.2017.4144. Epub 2018 Aug 23.


Ginsenoside Rg3, a bioactive constituent from Panax ginseng, is a worldwide well-known traditional Chinese medicine used as a tonic. It also has good antitumor activity by inhibiting tumors metastasis. Tumor metastasis is a high risk in thyroid cancer. However, the effect and molecular mechanism underlying the antimetastatic activity of Rg3 in thyroid cancer have not been reported. In our study, we found that Rg3 inhibited the growth of thyroid cancer in vitro and in vivo and significantly inhibited metastasis of thyroid cancer. Rg3 apparently inhibited the migration and invasion in four papillary thyroid cancer (PTC) cells (TPC-1, BCPAP, C643, and Ocut-2c cells) and pulmonary metastasis in lung metastasis model of C643 cells in nude mice. We further found that a possible mechanism of Rg3 inhibiting thyroid cancer cells metastasis was associated with inhibiting cells actin skeleton function. Rg3 inhibited lamellipodia formation and induced microspike formation by inhibiting Rho GTPase in thyroid cancer cells. Rg3 decreased the levels of Rac-1 and Cdc42 proteins. In addition, Rg3 decreased the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins in four thyroid cancer cells. The results that Rg3 remarkably inhibited the expression of vascular endothelial growth factor-C (VEGF-C) protein in PTC cells and VEGF-A protein in anaplastic thyroid cancer (ATC) cells and decreased the staining of CD31 in PTC and ATC tumors hinted that Rg3 might inhibit the lymph node metastasis in PTC and angiogenesis in ATC. These studies suggested that Rg3 might be a useful agent for the treatment of metastatic thyroid cancers.

Keywords: actin skeleton; ginsenoside Rg3; metastasis; thyroid cancer.

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Female
  • Ginsenosides / administration & dosage*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Metastasis
  • Panax / chemistry
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism


  • Actins
  • Antineoplastic Agents, Phytogenic
  • Ginsenosides
  • Vascular Endothelial Growth Factor A
  • ginsenoside Rg3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein