BRYOSTATIN 1-TAMOXIFEN COMBINATIONS SHOW SYNERGISTIC EFFECTS ON THE INHIBITION OF GROWTH OF P388 CELLS IN-VITRO

This study shows that combinations of bryostatin 1, a novel modulator of protein kinase C currently under clinical evaluation, with the anti -oestrogenic agent tamoxifen caused a large synergistic enhancement of growth inhibition in P388 cells in vitro. The growth-inhibitory effec ts of bryostatin 1 in the presence of non-inhibitory concentrations of tamoxifen were increased by approximately 200-fold, whereas growth in hibition by tamoxifen in the presence of non-inhibitory concentrations of bryostatin 1 were increased over 30-fold. These data have been con firmed by isobologram analysis. The precise mechanism underlying this effect is unknown, although preliminary data implicating protein kinas e C is presented. The magnitude of this synergistic effect, together w ith evidence of clinical responses seen when these agents were given s equentially in ovarian cancer, merits further study.