Picropodophyllin inhibits type I endometrial cancer cell proliferation via disruption of the PI3K/Akt pathway.

Abstract

The type-I insulin-like growth factor receptor (IGF-IR) is overexpressed in endometrial cancer. High IGF-IR expression was considered as an important prognostic factor for tumor progression. The purpose of this study was to investigate the role and molecular mechanism of IGF-IR inhibitor picropodophyllin (PPP) in the growth and development of endometrial cancer. High expression of IGF-IR was observed in endometrial cancer tissues, as well as in ECC-1 and KLE cell lines. PPP suppressed the number of clones of ECC-1 and KLE cell lines; however, it had no significant effect on HEC-1-A cell line, which expressed lower IGF-IR than ECC-1 and KLE cell lines. Furthermore, PPP reduced cell proliferation capacity, inhibited the IGF-IR mRNA expression, and suppressed protein phosphorylation of IGF-IR and Akt in the three cell lines. In addition, PPP inhibited the protein expression of survivin in KLE cell line after 1h of exposure, though this effect did not last for prolonged time. In conclusion, IGF-IR was mostly overexpressed in type I endometrial cancer. High IGF-IR expression was an important prognostic factor of tumor progression. PPP mediated the down-regulation of IGF-IR phosphorylation and inhibited cell proliferation via the PI3K/Akt signal pathway. PPP may have the potential to become a clinical treatment target in endometrial carcinoma.