Tamoxifen inhibits hepatoma cell growth through an estrogen receptor independent mechanism

Abstract

Abstract Background/Aims: Tamoxifen has previously been shown to prolong the survival of patients with advanced stages of hepatocellular carcinoma and it has been suggested that it inhibits the growth of hepatoma cells through an estrogen receptor-dependent mechanism. We have studied the effects of the synthetic estrogen, mestranol, and the antiestrogen, tamoxifen, on the growth regulation of hepatoma cells in vitro . Methods: Cells were maintained under fully estrogenized conditions and were deprived of estrogen shortly before conducting experiments. Results: In the human hepatoma cell line Hep 3B, tamoxifen inhibited cell growth in a concentration and time-dependent manner with effective concentrations ranging from 0.1 μM to 10 μM. Mestranol inhibited cell growth at a concentration of 10 μM and had an additive effect with tamoxifen on growth inhibition. Expression of estrogen receptors in hepatoma cells was not detected by enzyme immunoassay, Northern blot analysis or reporter gene expression assay. Furthermore, the introduction of estrogen receptors into Hep 3B cells did not alter the effect of tamoxifen and mestranol on cell growth. Conclusions: This study suggests that tamoxifen inhibits the growth of Hep 3B hepatoma cells through an estrogen receptor-independent mechanism.