Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components

Int J Oncol. 1999 Jul;15(1):33-9. doi: 10.3892/ijo.15.1.33.

Abstract

Integrins play an important role in tumor dissemination. The purpose of this study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix components. Activated lansoprazole (AG-2000) was used as the SH-reactive reagent because this compound is known to react with SH groups but does not permeate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cells to matrix was examined, using both an in vitro adhesion assay and an in vivo nude mouse xenograft model of peritoneal implantation. In the in vitro adhesion assay, a 60-min exposure of AsPC-1 cells to AG-2000 resulted in a dose-dependent inhibition of AsPC-1 cell adhesion to laminin, fibronectin and type IV collagen, although AG-2000 did not affect the viability of AsPC-1 cells by MTT assay. In the in vivo assessment of AsPC-1 cell implantation, the AsPC-1 cells were initially preincubated with AG-2000 for 60 min to ensure adequate exposure of the AsPC-1 cells to AG-2000 before intraperitoneal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short exposure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracellular matrix components.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / therapeutic use
  • Cell Adhesion / drug effects*
  • Extracellular Matrix / metabolism
  • Humans
  • Injections, Intraperitoneal
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects*
  • Omentum
  • Pancreatic Neoplasms / pathology
  • Peritoneal Neoplasms / prevention & control
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use
  • Sulfhydryl Reagents / pharmacology*
  • Sulfhydryl Reagents / therapeutic use
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Pyridines
  • Sulfhydryl Reagents
  • AG 2000