Studies on the proliferative activity of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in cancer cells have shown that both peptides can affect cell growth depending on a model system, time of incubation or the peptides concentration used (Sokolowska and NowaK 2008). Changes in cellular microenvironment caused by trophic factor deprivation interfere with cancer progression, acting on cell-to-cell interactions between cancer cells and their ability to proliferate (Longo et al., 2010). However, it is not known whether trophic factor removal may have an impact on PACAP and VIP affect malignancy of glioma cells. In the present study, using an in vitro model mimicking microenvironmental changes related to trophic factor deprivation, we explored the effects of both PACAP or VIP on C6 glioma cells grown either in normal growth medium (10%FBS) or in serum-free medium. Cell proliferation and expression of proteins related to cell malignancy (GFAP and nestin) were assessed by MTT assay, immunoblot and confocal microscopy analysis. Results demonstrated that serum deprivation and, to a greater extent, the treatment with PACAP or VIP decreased cellular proliferation and nestin protein expression. In conclusion, these results suggest that both peptides enhance the effects of serum deprivation on cell growth and malignancy. These data also confirm previous studies demonstrating that Nestin expression might change in cancer cells as a result of environmental signaling.
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