Tamoxifen lowers the MMP-9/TIMP-1 ratio and inhibits the invasion capacity of ER-positive non-small cell lung cancer cells

Biomed Pharmacother. 2011 Oct;65(7):525-8. doi: 10.1016/j.biopha.2011.06.002. Epub 2011 Aug 25.


Tamoxifen (TAM) serves for decades as a therapy drug for the prevention and treatment of breast cancers, especially effective for the estrogen receptor (ER)-positive ones. An increasing number of studies are trying to explore its potential application in treating other types of tumor including lung cancer. However, the effects of TAM on lung cancer cells, especially ER-positive ones, remain unclear. Thus, the present study was undertaken to assess the impact of TAM on the invasion capacity of an ER-positive human lung cancer cell model. In this study, the immunohistochemical staining was applied to verify the expression of estrogen receptors in SPC-A-1, a human lung adenocarcinoma cell line. The real-time PCR analysis was performed to test the expressions of MMP-9 and TIMP-1 in SPC-A-1 cells treated with different doses of TAM, while the invasion capacity was determined using transwell assays. In TAM-treated SPC-A-1 cells, which are ER-positive, an impaired ratio of MMP-9/TIMP-1 was observed as a net result of an increased transcriptional level of TIMP-1 as well as a reduced one of MMP-9. Furthermore, TAM suppressed the invasion of SPC-A-1 cells in vitro. Thus, we propose that TAM could work as an anti-metastasis drug inhibiting the invasion of human lung cancer cells.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / enzymology
  • Collagen
  • Drug Combinations
  • Drug Screening Assays, Antitumor
  • Enzyme Induction / drug effects
  • Estrogens*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Laminin
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • MCF-7 Cells / drug effects
  • MCF-7 Cells / enzymology
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Neoplasm Invasiveness*
  • Neoplasm Proteins / analysis*
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / enzymology
  • Neoplasms, Hormone-Dependent / pathology*
  • Proteoglycans
  • Real-Time Polymerase Chain Reaction
  • Receptors, Estrogen / analysis*
  • Tamoxifen / pharmacology*
  • Tamoxifen / therapeutic use
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics


  • Antineoplastic Agents, Hormonal
  • Drug Combinations
  • Estrogens
  • Laminin
  • Neoplasm Proteins
  • Proteoglycans
  • Receptors, Estrogen
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tamoxifen
  • matrigel
  • Collagen
  • Matrix Metalloproteinase 9