The standard treatment for advanced
pancreatic cancer is
chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this
malignancy is urgently required. In the present study, the anticancer effect of
arsenite on
platelet-derived growth factor (
PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in
pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay,
arsenite clearly inhibited
PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells.
Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of
cyclin D1 and phosphorylated
retinoblastoma protein decreased following treatment with
arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of
arsenite on upstream p44/
p42 mitogen-activated protein kinase (MAPK) and Akt was investigated.
PDGF-BB caused phosphorylation of p44/
p42 MAPK and Akt in both cell lines. Pretreatment with
arsenite significantly suppressed
PDGF-BB-induced phosphorylation of Akt, but not of p44/
p42 MAPK in AsPC-1 cells. By contrast,
arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced
PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that
arsenite inhibits
PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore,
arsenite may be a useful tool for the treatment of patients with certain types of
pancreatic cancer, without causing adverse effects on normal pancreatic cells.