Suppression of pancreatic tumor progression by systemic delivery of a pancreatic-cancer-specific promoter driven Bik mutant

Cancer Lett. 2006 May 8;236(1):58-63. doi: 10.1016/j.canlet.2005.05.001. Epub 2005 Jun 13.

Abstract

Pancreatic cancer is highly aggressive with extremely poor prognosis. Developing a pancreatic cancer specific promoter (PCSP) is one approach for pancreatic cancer gene therapy. We have modified the promoter of cholecystokinin type A receptor (CCKAR), named CCK/Mpd, which possesses a relatively high activity in pancreatic cancer cells as compared with normal cells. The CCK/Mpd promoter-driven luciferase exhibits a better tumor specific tissue distribution than the CMV promoter-driven luciferase when systemically administered in vivo. Notably, we demonstrate a treatment efficacy by using CCK/Mpd-Bik-DD/liposome in a nude mice xenograft model, suggesting the feasibility of PCSP-based gene therapy in pancreatic cancer treatment.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Genetic Therapy / methods
  • Humans
  • Liposomes
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Mice, Nude
  • Mutation
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Promoter Regions, Genetic*
  • Receptor, Cholecystokinin A / administration & dosage
  • Receptor, Cholecystokinin A / genetics*
  • Receptor, Cholecystokinin A / metabolism
  • Tissue Distribution
  • Transfection

Substances

  • Apoptosis Regulatory Proteins
  • Liposomes
  • Receptor, Cholecystokinin A
  • Luciferases