Effect of cyclophilin A on gene expression in human pancreatic cancer cells

Am J Surg. 2005 Nov;190(5):739-45. doi: 10.1016/j.amjsurg.2005.07.013.


Background: We previously found that cyclophilin A (CypA) is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. In this study, we further investigated the effect of CypA on gene expression of several key molecules that are involved in pancreatic cancer cell proliferation.

Methods: Human pancreatic cancer cell lines (Panc-1, MIA PaCa-2, and BxPC-3) and human pancreatic ductal epithelial (HPDE) cells were used. The messenger RNA (mRNA) levels of CypA, CypB, CD147, neuropilins (NRPs), vascular endothelial growth factor (VEGF), and VEGF receptors upon the treatment of exogenous recombinant human CypA were determined by real-time reverse-transcription polymerase chain reaction.

Results: Exogenous human recombinant CypA reduced the mRNA levels of NRP-1 and VEGF, but not endogenous CypA, CypB, and CD147, in Panc-1, MIA PaCa-2, and BxPC-3 cells. In contrast, HPDE cells showed a decrease of endogenous CypA and CD147 mRNA, but not detectable changes of CypB, NRPs, and VEGF mRNA levels upon exogenous CypA treatment.

Conclusions: These data show that exogenous CypA downregulates NRP-1 and VEGF expression in pancreatic cancer cells. This effect is different in normal HPDE cells. Thus, soluble CypA may affect cell growth of pancreatic cancer.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Basigin
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclosporine / pharmacology*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • In Vitro Techniques
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Antigens, CD
  • BSG protein, human
  • Immunosuppressive Agents
  • RNA, Messenger
  • RNA, Neoplasm
  • Vascular Endothelial Growth Factor A
  • Basigin
  • Neuropilin-1
  • Cyclosporine