Influence of tamoxifen on the level of cellular proliferation on cultured human pituitary adenoma cells and its mechanism / 中国药理学通报

ABSTRACT

Aim To investigate the effects of tamoxifen on the proliferation and DNA synthesis of cultured human pituitary adenoma cells and make a further investigation of the mechanism of the inhibitory effect of tamoxifen on the proliferation of pituitary adenoma cells. Methods The techniques of MTT colorimetry, 3H-TdR, flow cytometry, PKC activity detection and cAMP/ cGMP levels detection were used to detect or observe the effects of tamoxifen on proliferation, DNA synthesis, cell cycle, PKC activity and cAMP/ cGMP levels of cultured human pituitary adenoma cells, respectively.Results ①Tamoxifen (0.1,1 and 10 ?mol?L -1) inhibited the proliferation and DNA synthesis of cultured human pituitary adenoma cells in a dose-dependent manner.② tamoxifen (1,10 and 20 ?mol?L -1) increased the ratio of G_1 phase of pituitary adenoma cells, and decreased the ratio of S and G_2 phase markedly;②compared with control, PMA, a PKC activator, increased the activity of membrane and total PKC in human pituitary adenoma cells. However, after a 15-min treatment with tamoxifen (10 ?mol?L -1),a significant reduction of the activity of cytoplasm, membrane and total PKC in human pituitary adenoma cells was observed;③tamoxifen (1 and 10 ?mol?L -1) increased the amount of cAMP in the cytoplasm of human pituitary adenoma cells, but had no effect on that of cGMP. Conclusion These data provide an important clue to explore the molecular mechanisms of the inhibitory effect of tamoxifen on the proliferation of pituitary adenoma cells, and suggest that the modulating effect of tamoxifen on the proliferation of pituitary adenoma cells results from interactions of several cellular signaling pathways.