Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components

Integrins play an important role in tumor dissemination. The purpose of thi s study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix com ponents. Activated lansoprazole (AG-2000) was used as the SH-reactive reage nt because this compound is known to react with SH groups but does not perm eate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cel ls 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 implantatio n, 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 intraperiton eal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short expos ure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracel lular matrix components.