INHIBITION OF TUMOR-CELL PLATELET INTERACTIONS AND TUMOR-METASTASIS BY THE CALCIUM-CHANNEL BLOCKER, NIMODIPINE
INHIBITION OF TUMOR-CELL PLATELET INTERACTIONS AND TUMOR-METASTASIS BY THE CALCIUM-CHANNEL BLOCKER, NIMODIPINE
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DOI：
10.1007/bf00132307
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发表时间：
1984-01-01
影响因子：
4
通讯作者：
SLOANE, BF
中科院分区：
文献类型：
--
作者：
HONN, KV;ONODA, JM;SLOANE, BF
体外评价了二氢吡啶类钙通道阻滞剂尼莫地平对B16无色素性黑色素瘤(B16a)和Walker 256癌肉瘤(W256)细胞诱导的血小板聚集的抑制作用，以及对B16a和W256与大鼠微血管内皮细胞黏附的抑制作用。尼莫地平对肿瘤细胞诱导的血小板聚集(TCIPA)有剂量依赖性抑制作用。无论有无明显的血小板聚集，血小板均可增强肿瘤细胞与内皮细胞的粘附性。然而，最大的粘附性增强发生在聚集条件下。在聚集性和非聚集性条件下，尼莫地平40微克/毫升可抑制血小板增强的内皮细胞黏附。尼莫地平被活体测试为其抑制实验性和自发性转移的能力。尼莫地平在5 mg/kg体重时对肺集落形成有46%的抑制作用。在0.1-80 mg/kg的剂量范围内，尼莫地平对皮下肿瘤肺转移的形成有显著的剂量依赖性抑制作用。体外实验结果表明，二氢吡啶钙通道阻滞剂可以抑制肿瘤细胞-血小板-内皮细胞的相互作用。活体实验结果提示，这些化合物可能是一类新的抗肿瘤转移药物。
Nimodipine, a dihydropyridine calcium channel blocker, was evaluatedin vitrofor its ability to inhibit platelet aggregation induced by B 16 amelanotic melanoma (B16a) and Walker 256 carcinosarcoma (W256) cells, and for its ability to inhibit platelet-enhanced B16a and W256 adhesion to rat microvascular endothelial cells. Nimodipine produced a dose-dependent inhibition of tumor-cell-induced platelet aggregation (TCIPA). Platelets enhanced tumor cell adhesion to endothelium both in the presence and absence of overt platelet aggregation. However, the greatest enhancement of adhesion occurred under aggregatory conditions. Nimodipine at a dose of 40 µg/ml inhibited platelet-enhanced adhesion to endothelium under aggregatory and nonaggregatory conditions. Nimodipine was testedin vivofor its ability to inhibit both ‘experimental’ and spontaneous metastasis. Nimodipine produced a 46 per cent inhibition of lung colony formation at a dose of 5 mg/kg body-weight. Over a dose range of 0·1–80 mg/kg, nimodipine produced a significant dose-dependent inhibition in the formation of lung metastases from a subcutaneous tumor. Thein vitroresults demonstrate that a dihydropyridine calcium channel blocker can inhibit tumor cell-platelet-endothelial cell interactions. Thein vivoresults suggest that these compounds may be a new class of antimetastatic agent.