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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 1 h 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.