PMID: 20651347Jul 24, 2010Paper

Antiproliferative effects of antiestrogens and inhibitors of growth factor receptor signaling on endometrial cancer cells

Anticancer Research
Martin BlockAndreas R Günthert

Abstract

In patients with advanced estrogen-dependent type I endometrial cancer (EC), pharmacological treatment with progestins or antiestrogens is recommended, but primary and secondary resistance are common. The aim of our study was to investigate single-agent and dual-agent therapeutic strategies in estrogen receptor-positive human EC cells. Human EC cells Ishikawa and HEC1A were cultivated under estrogen-reduced conditions and exposed to 4-hydroxytamoxifen (OHT), fulvestrant, gefitinib, everolimus, and the AKT inhibitor perifosine. Effects of drugs were analyzed by proliferation and apoptosis assays. Additionally, we analyzed expression of aromatase, phosphatase and tensin homolog (PTEN), AKT and pAKT and G protein-coupled receptor 30 (GPR30). Neither OHT nor fulvestrant inhibited cell growth, nor did they induce apoptosis. Gefitinib, everolimus and perifosine inhibited proliferation in all cell lines. Only perifosine induced apoptosis. In PTEN-positive HEC1A cells, combined treatment of gefitinib plus OHT showed increased antiproliferative effects. In Ishikawa cells, combined treatment of everolimus plus gefitinib had synergistic antiproliferative effects. The most effective single-agent treatment and the only drug that induced apo...Continue Reading

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