Thalidomide down-regulates the expression of VEGF and bFGF in cisplatin-resistant human lung carcinoma cells

Anticancer Res. May-Jun 2003;23(3B):2481-7.

Abstract

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancer. Thalidomide (alpha-N-phthalimidoglutarimide) is a potent inhibitor of angiogenesis, and it is reported to overcome classical drug resistance in human multiple myeloma cells. However, the effect of this agent on the expression of angiogenic growth factors in cisplatin-resistant tumors is largely unknown. In the current study, we showed that thalidomide suppressed the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cisplatin-resistant human A549DDP lung carcinoma cells. The mRNA levels of VEGF and bFGF were markedly decreased in the A549DDP cells treated with the therapeutic concentrations of thalidomide (0.6-6 micrograms/ml), as determined by RT-PCR analysis. Consistent with these results, thalidomide also significantly reduced the protein levels of VEGF and bFGF in these cells in a dose- and time-dependent manner. This study provided evidence to support the potential therapeutic applications of thalidomide in cisplatin-resistant human lung cancer and other tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Angiogenesis Inhibitors / pharmacology*
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm
  • Endothelial Growth Factors / antagonists & inhibitors
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / biosynthesis*
  • Fibroblast Growth Factor 2 / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lymphokines / antagonists & inhibitors
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thalidomide / pharmacology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Angiogenesis Inhibitors
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • Thalidomide
  • Cisplatin