Inhibition of PDGFRβ in colorectal cancer cells leads to decreased proliferation and G2 cell cycle arrest

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the western world and growth factors and their receptors play a significant role in the regulation of CRC growth, angiogenesis, and metastasis. The platelet-derived growth factor receptor (PDGFR) has attracted increasing attention as potential target of anti-tumor therapy in CRC. In the present study the influence of the α- and β-subunit of the PDGFR (PDGFRα, -β) was investigated in different CRC cell lines. PDGFRα expression was not observed in all cell lines tested, however, varying expression levels of PDGFRβ could be detected both at the RNA and the protein level in the cell lines CaCo-2, DLD-1, SW480 and SW837. To study the function of PDGFRß in CRC cell lines, SW480 cells showing the highest PDGFRß expression were used for receptor blockade. The inhibition was performed by two different strategies: firstly, PDGFRß expression was down-regulated by three different PDGFRß-specific siRNAs. Secondly, the tyrosine kinase activity of the PDGFRß receptor was inhibited by the pharmacological inhibitor Ki11502. Both approaches of PDGFRß inhibition resulted in a significant decrease of SW480 cell proliferation, whereas an increased rate of apoptosis could not be detected. Both the treatment with the PDGFRß-specific siRNAs as well as with the inhibitor Ki11502 resulted in a reduced activity of the PI3K signaling cascade, while the MAPK signaling cascade was not affected. Further experiments showed that the treatment with the PDGFRß inhibitor led to a G2 arrest in SW480 cell cycle progression. Taken together, these results support the assumption that PDGFRß could act as a potential therapeutical target in CRC treatment.