Thalidomide Distinctly Affected TNF-α, IL-6 and MMP Secretion by an Ovarian Cancer Cell Line (SKOV-3) and Primary Ovarian Cancer Cells

Eur Cytokine Netw. Jul-Sep 2013;24(3):122-9. doi: 10.1684/ecn.2013.0342.

Abstract

Background: Thalidomide inhibits TNF-α production in lipopolysaccharide-stimulated monocytes. The aim of this study was to evaluate the effect of thalidomide on TNF-α, IL-6 and MMP secretion in epithelial ovarian carcinoma cells.

Materials and methods: SKOV-3 cells and primary epithelial ovarian carcinoma cells were cultured in the presence of various concentrations of thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF-α and IL-6 levels were determined in the supernatants of the cell cultures by ELISA, and MMP activity was examined by gelatin zymography.

Results: Thalidomide did not significantly affect the proliferation and growth of SKOV-3 cells. However, it decreased significantly the capacity of SKOV-3 cells and primary epithelial ovarian carcinoma cells to secrete TNF-α. Thalidomide also significantly decreased the capacity of SKOV-3 cells, but not primary epithelial ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma cells.

Conclusion: Our study suggests that thalidomide distinctly affected TNF-α, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and primary ovarian cancer cells. This might suggest a different susceptibility of these two types of cells to thalidomide, and/or that the mechanisms of secretion of the factors examined are differently regulated in these cells. Our results may deepen our understanding the mechanism/s of action of thalidomide in ovarian carcinoma cells. The results might have important implications in future therapeutic strategies that will incorporate thalidomide and other cytokine inhibitors in the treatment of epithelial ovarian carcinoma.

Keywords: IL-6; MMP; TNF-α; ovarian cancer; thalidomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-6 / metabolism*
  • Metalloendopeptidases / metabolism*
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Thalidomide / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Immunosuppressive Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • Metalloendopeptidases