Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity

PLoS One. 2015 May 21;10(5):e0127778. doi: 10.1371/journal.pone.0127778. eCollection 2015.

Abstract

The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / metabolism*
  • Carcinoma, Lewis Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chalcones / administration & dosage
  • Chalcones / pharmacology*
  • Disease Models, Animal
  • Enzyme Activation
  • Gene Expression
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Mice
  • Neoplasm Metastasis
  • Phosphorylation
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Cadherins
  • Chalcones
  • TOR Serine-Threonine Kinases
  • cardamonin

Grants and funding

This work was supported by the Natural Science Foundation of Fujian Province (NO. 2012J01312). The URL of the funder is http://xmgl.fjkjt.gov.cn/. DHS received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.