Suppressive effects of exogenous regucalcin on the proliferation of human pancreatic cancer MIA PaCa-2 cells in vitro.

Abstract

Regucalcin plays a pivotal role as a suppressor protein in signal transduction in various types of cells and tissues. The regucalcin gene is localized on the X chromosome. and its expression has been shown to be suppressed in various types of tumor tissue in animal and human subjects, suggesting a potential role of regucalcin in carcinogenesis. This study was undertaken to determine the effects of exogenous regucalcin on the proliferation of cloned human pancreatic cancer MIA PaCa-2 cells in vitro. The proliferation of the MIA PaCa-2 cells was suppressed following culture with regucalcin (0.01-10 nM). Such an effect was also observed in pancreatic cancer Pt45P1 cells, that highly expressed tissue factor (high TF), or Pt45P1 cells, that highly expressed alternativly spliced variants of tissue factor (asTF). In the MIA PaCa-2 cells, the suppressive effects of regucalcin on cell proliferation were not enhanced either in the presence of tumor necrosis factor-α (TNF-α), or in the presence of Bay K 8644, PD98059, staurosporine, wortmannin or 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB). However, this was not the case for gemcitabine, which was shown to suppress cell proliferation. Exogenous regucalcin did not cause apoptotic cell death in the MIA PaCa-2 cells in vitro. These findings demonstrate that exogenous regucalcin exerts suppressive effects on the proliferation of human pancreatic MIA PaCa-2 cells and that these effects are mediated through the inhibition of various signaling pathways related to nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK), protein kinase C, calcium signaling, phosphatidylinositol 3-kinase (PI3K) or nuclear transcription activity in vitro. Our data suggest that exogenous regucalcin exerts suppressive effects on the proliferation of human pancreatic cancer cells.