Effect of verapamil on cell cycle transit and c-myc gene expression in normal and malignant murine cells.
Effect of verapamil on cell cycle transit and c-myc gene expression in normal and malignant murine cells.
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DOI：
10.1038/bjc.1989.150
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发表时间：
1989-05
影响因子：
8.8
通讯作者：
Ettinger, R S
中科院分区：
文献类型：
--
作者：
Huber, K R;Schmidt, W F;Thompson, E A;Forsthoefel, A M;Neuberg, R W;Ettinger, R S
维拉帕米是钙通道阻滞剂的原型，可可逆地抑制许多正常和肿瘤细胞系的细胞增殖（Schmidt et al., Cancer Res., 48,3617,1988）。我们发现了两个密切相关的细胞系——B16小鼠黑色素瘤细胞和B10。在培养中生长的正常小鼠黑素细胞在维拉帕米存在下表现不同，我们现在利用这两种相关细胞系来帮助阐明维拉帕米抗增殖作用的分子基础。在本研究中，我们研究了两种细胞系在不含维拉帕米的情况下、维拉帕米孵育期间和洗去维拉帕米后的细胞周期期分布和c-myc基因表达。我们的研究表明，100微米维拉帕米能迅速阻断黑素细胞的DNA合成，但对B16细胞没有作用。同样，维拉帕米6-24小时孵育后，黑素细胞中的c-myc信号降低，但B16细胞中的c-myc表达会短暂增加。与药物孵育24小时后，维拉帕米从细胞中洗净后，黑色素细胞开始再次增殖时c-myc表达增加，但B16细胞开始死亡时c-myc表达减少。我们对这些细胞系的不同结果表明，c-myc基因表达，不管其已知参与生长控制，不是维拉帕米抑制作用的直接目标。
Verapamil, the prototype calcium channel blocker, reversibly inhibits cell proliferation in many normal and tumour cell lines (Schmidt et al., Cancer Res., 48, 3617, 1988). We have found that two closely related cell lines - B16 murine melanoma cells and B10.BR normal murine melanocytes growing in culture - behave differently in the presence of verapamil, and we are now utilising these two related cell lines to help elucidate the molecular basis of verapamil's antiproliferative effect. In this study, we studied cell cycle phase distribution and c-myc gene expression in both cell lines in the absence of verapamil, during incubation with verapamil and after the cells were washed free of verapamil. Our studies show that 100 microM verapamil rapidly blocks DNA synthesis in melanocytes but not in B16 cells. Similarly, incubation with verapamil for 6-24 h results in a decreased c-myc signal in melanocytes, but a transient increase in c-myc expression in B16 cells. After verapamil is washed from the cells following a 24-h incubation with drug, c-myc expression increases in melanocytes as they begin again to proliferate, but decreases in B16 cells as they begin to die. Our disparate results with these cell lines suggest that c-myc gene expression, regardless of its known involvement in growth control, is not the immediate target for verapamil's inhibitory action.