Rouzaire-Dubois B, Dubois J M
Laboratoire de Physiologie Comparée, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Cell Signal. 1990;2(4):387-93. doi: 10.1016/0898-6568(90)90069-m.
The effects of tamoxifen (TAM) on cell proliferation and voltage-dependent K+ channels were studied on the mouse neuroblastoma cells NG 108-15. TAM inhibited cell proliferation with an effective dose inducing a half maximum effect (ED50) of 2 microM and was cytotoxic from and beyond 2.5 microM. TAM accelerated the apparent inactivation of the whole cell K+ current with an apparent dissociation constant of 0.46 microM, and shifted the peak K+ conductance-voltage curve towards negative voltages with an apparent dissociation constant of 1.07 microM. The K+ flux at the resting potential, calculated from the time integral of the K+ current recorded during depolarizations, was decreased by TAM. The effect of TAM on the cell proliferation was perfectly correlated with the effect of TAM on the resting K+ flux. The results suggest that cell mitosis is, in some way, controlled by the functioning of K+ channels and that the antitumour action of tamoxifen could be due to its interaction with K+ channels.
在小鼠神经母细胞瘤细胞NG 108 - 15上研究了他莫昔芬（TAM）对细胞增殖和电压依赖性钾通道的影响。TAM抑制细胞增殖，其诱导半数最大效应的有效剂量（ED50）为2微摩尔，且在2.5微摩尔及以上时具有细胞毒性。TAM加速了全细胞钾电流的表观失活，其表观解离常数为0.46微摩尔，并使钾电导-电压曲线的峰值向负电压方向移动，表观解离常数为1.07微摩尔。根据去极化期间记录的钾电流的时间积分计算得出的静息电位下的钾通量，被TAM降低。TAM对细胞增殖的作用与TAM对静息钾通量的作用完全相关。结果表明，细胞有丝分裂在某种程度上受钾通道功能的控制，且他莫昔芬的抗肿瘤作用可能归因于其与钾通道的相互作用。
