Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells

Radiother Oncol. 2009 Sep;92(3):362-70. doi: 10.1016/j.radonc.2009.07.004. Epub 2009 Aug 6.


Background and purpose: Resistance of pancreatic ductal adenocarcinoma (PDAC) to chemo- and radiotherapy is a major obstacle. The integral membrane protein Caveolin-1 (Cav-1) has been suggested as a potent target in human pancreatic carcinoma cells.

Materials and methods: Human pancreatic tumor cells were examined in a three-dimensional (3D) cell culture model with regard to clonogenic survival, apoptosis, radiogenic DNA-double strand breaks and protein expression and phosphorylation under siRNA-mediated knockdown of Cav-1 without and in combination with irradiation (X-rays, 0-6Gy). Immunohistochemistry was used to assess Cav-1 expression in biopsies from patients with PDAC.

Results: Tumor cells in PDAC showed significantly higher Cav-1 expression relative to tumor stroma. Cav-1 knockdown significantly reduced beta1 integrin expression and Akt phosphorylation, induced Caspase 3- and Caspase 8-dependent apoptosis and enhanced the radiosensitivity of 3D cell cultures. While cell cycling and Cav-1 promoter activity remained stable, Cav-1 knockdown-induced radiosensitization correlated with elevated numbers of residual DNA-double strand breaks.

Conclusions: Our data strongly support the concept of Cav-1 as a potent target in pancreatic carcinoma cells due to radiosensitization and Cav-1 overexpression in tumor cells of PDAC. 3D cell cultures are powerful and useful tools for the testing of novel targeting strategies to optimize conventional radio- and chemotherapy regimes for PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / radiotherapy
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects*
  • Cell Line, Tumor / cytology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / radiotherapy
  • Phosphorylation / genetics
  • Phosphorylation / radiation effects
  • Probability
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Radiation Tolerance*
  • Radiation, Ionizing
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stem Cells / drug effects
  • Stem Cells / radiation effects
  • Transfection


  • Caveolin 1
  • Integrin beta1
  • RNA, Small Interfering