Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components.
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.
Ohta
T
T
Department of Surgery (II), School of Medicine, Kanazawa University, Kanazawa 920-0934, Japan.
Tajima
H
H
Yachie
A
A
Yokoyama
K
K
Elnemr
A
A
Fushida
S
S
Kitagawa
H
H
Kayahara
M
M
Nishimura
G
G
Miwa
K
K
Yamamoto
M
M
Terada
T
T
Ohkuma
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D009852:Omentum; D010190:Pancreatic Neoplasms / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D013439:Sulfhydryl Reagents / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011725:Pyridines; D013439:Sulfhydryl Reagents; C058689:AG 2000