McGown A T, Jayson G, Pettit G R, Haran M S, Ward T H, Crowther D
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Br J Cancer. 1998;77(2):216-20. doi: 10.1038/bjc.1998.36.
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 effects of bryostatin 1 in the presence of non-inhibitory concentrations of tamoxifen were increased by approximately 200-fold, whereas growth inhibition by tamoxifen in the presence of non-inhibitory concentrations of bryostatin 1 were increased over 30-fold. These data have been confirmed by isobologram analysis. The precise mechanism underlying this effect is unknown, although preliminary data implicating protein kinase C is presented. The magnitude of this synergistic effect, together with evidence of clinical responses seen when these agents were given sequentially in ovarian cancer, merits further study.
本研究表明,目前正在进行临床评估的新型蛋白激酶C调节剂苔藓抑素1与抗雌激素药物他莫昔芬联合使用,在体外对P388细胞的生长抑制具有显著的协同增强作用。在非抑制浓度的他莫昔芬存在下,苔藓抑素1的生长抑制作用增加了约200倍,而在非抑制浓度的苔藓抑素1存在下,他莫昔芬的生长抑制作用增加了30倍以上。这些数据已通过等效线图分析得到证实。尽管已提供了涉及蛋白激酶C的初步数据,但这种作用的确切机制尚不清楚。这种协同作用的程度,以及这些药物在卵巢癌中序贯给药时观察到的临床反应证据,值得进一步研究。