ag-2000 and Peritoneal-Neoplasms

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.

Topics: Animals; Antineoplastic Agents; Benzimidazoles; Cell Adhesion; Extracellular Matrix; Humans; Injections, Intraperitoneal; Mice; Mice, Nude; Neoplasm Transplantation; Neoplastic Stem Cells; Omentum; Pancreatic Neoplasms; Peritoneal Neoplasms; Pyridines; Sulfhydryl Reagents; Tumor Cells, Cultured