IGF-IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway

Type 1 insulin-like growth factor receptor (IGF-IR) signaling is considered to serve a key role in the development of cancer. However, the effects of IGF-IR on the malignant characteristics of myelodysplastic syndrome (MDS) clonal cells remains to be determined. In the present study it was demonstrated that knockdown of IGF-IR reduced the proliferation and increased the apoptosis of MDS/leukemia cells. Integrated analysis of gene expression profiles using bioinformatics identified the MAPK signaling pathway as a critical downstream factor of IGF-IR, and this was confirmed in vitro using western blotting which revealed that IGF-IR knockdown significantly increased the expression of activated MAPK. Furthermore, IGF-IR signaling was inhibited to investigate the potential of IGF-IR as a therapeutic target of MDS. The results revealed that the IGF-IR inhibitor picropodophyllin (PPP) inhibited cell proliferation, promoted cell apoptosis and arrested the cell cycle at the G2/M phase in MDS/leukemia cells. Similar to the effects of IGF-IR knockdown, PPP treatment also increased MAPK signaling in vitro. In conclusion, IGF-IR may serve as a potential therapeutic target of MDS.