维拉帕米在人肿瘤细胞和体外肿瘤细胞生长中不同程度地抑制激动剂诱导的Ca2+瞬态。

Invasion & metastasis Pub Date : 1996-01-01
A Brocchieri, A Saporiti, M Moroni, C Porta, A Tua, G Grignani
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引用次数: 0

摘要

已知血小板激动剂有助于调节肿瘤细胞的细胞质Ca2+水平,这种特性可能与刺激细胞增殖有关。在本研究中,我们研究了ADP、胶原蛋白和凝血酶在不同人类肿瘤细胞系(间皮瘤、ddd - 1a黑色素瘤、HeLa子宫癌)中增加细胞质Ca2+水平的能力,并分析了钙通道阻滞剂维拉帕米对Ca2+通量和体外肿瘤细胞生长的影响。ADP能诱导所有细胞系肿瘤细胞胞质Ca2+浓度瞬间升高;胶原蛋白在间皮瘤细胞和HeLa细胞中显示出这种作用,凝血酶仅在间皮瘤细胞中有效。维拉帕米以剂量依赖性的方式抑制有效激动剂诱导的Ca2+通量。adp诱导的Ca2+瞬间抑制的IC50值在间皮瘤细胞中为63.5微米,在DND-1A细胞中为97.3微米,在HeLa细胞中为93.5微米,而抑制胶原诱导的Ca2+运动的IC50值略高(间皮瘤细胞为170.2微米,HeLa细胞为112.3微米),抑制凝血酶诱导的Ca2+通量的IC50值(仅在间皮瘤细胞中评估)较低(22.5微米)。药物对肿瘤细胞体外生长的抑制作用呈剂量依赖性;生长抑制的IC50值在间皮瘤细胞为21.8 microM,在DND-1A细胞为9.1 microM,在HeLa细胞为6.4 microM,表明维拉帕米的抗增殖活性部分不依赖于Ca(2+)。这些数据可能有助于阐明肿瘤与止血系统双向相互作用的机制,并可能有助于确定新的药物控制策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth.

Platelet agonists are known to contribute to the regulation of cytoplasmic Ca2+ levels in tumor cells and this property could be relevant in the stimulation of cell proliferation. In the present study we investigated the ability of ADP, collagen and thrombin to increase cytoplasmic Ca2+ levels in different human tumor cell lines (mesothelioma, DND-1A melanoma, HeLa uterine carcinoma) and we analyzed the effect of the calcium channel blocker verapamil on Ca2+ fluxes and on in vitro tumor cell growth. ADP was able to induce a transient increase in the cytoplasmic Ca2+ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. Verapamil inhibited Ca2+ fluxes induced by the effective agonists in a dose-dependent manner. Values of IC50 for inhibition of ADP-induced Ca2+ transients were 63.5 microM in mesothelioma cells, 97.3 microM in DND-1A cells and 93.5 microM in HeLa cells, while those for inhibition of collagen-induced Ca2+ movements were slightly higher (170.2 microM in mesothelioma cells and 112.3 microM in HeLa cells) and the value of IC50 for inhibition of thrombin-induced Ca2+ fluxes (evaluated only in mesothelioma cells) was lower (22.5 microM). The drug dose-dependently also inhibited the in vitro growth of tumor cells; values of IC50 for growth inhibition were 21.8 microM in mesothelioma cells, 9.1 microM in DND-1A cells and 6.4 microM in HeLa cells, suggesting that the antiproliferative activity of verapamil was partly Ca(2+)-independent. These data may be of interest to elucidate the mechanisms of the two-way interactions of tumors with the hemostatic system and may help to identify new pharmacologic strategies for their control.

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