Lee Y S, Wurster R D
Department of Physiology, College of Medicine, Kwandong University, Kangreung, South Korea.
Cancer Lett. 1996 Dec 20;110(1-2):243-8. doi: 10.1016/s0304-3835(96)04518-1.
The possible interaction between antiestrogens (tamoxifen, clomiphene and nafoxidine) and bepridil, a known Na+-Ca2+ exchange blocker, in the regulation of cell growth was investigated using U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cells as model cellular systems. The co-treatment of bepridil with antiestrogens significantly enhanced the antiestrogen-induced inhibition of the tumor cell growth. This bepridil-induced enhanced growth inhibition was significantly blocked by the addition of BAPTA/AM, an intracellular Ca2+ chelator, implying that increased free intracellular Ca2+ concentration may be involved in these actions. Other Na+-Ca2+ exchange blockers such as nickel and benzamil, also significantly potentiated the antiestrogen-induced inhibition of the tumor cell growth. Taken together, the blockade of Na+-Ca2+ exchange mechanism by these drugs may cause prolongation of increased intracellular Ca2+ concentration, in turn leading to these potentiated growth inhibitions of the tumor cells. These results suggest that the combined treatment with bepridil and antiestrogens may be a potential strategy for chemotherapy of brain tumors.
以U-373 MG人星形细胞瘤和SK-N-MC人神经母细胞瘤细胞作为模型细胞系统，研究了抗雌激素药物（他莫昔芬、克罗米芬和萘福昔定）与已知的Na⁺-Ca²⁺交换阻滞剂苄普地尔在细胞生长调节中的可能相互作用。苄普地尔与抗雌激素药物联合处理显著增强了抗雌激素诱导的肿瘤细胞生长抑制作用。添加细胞内Ca²⁺螯合剂BAPTA/AM可显著阻断苄普地尔诱导的增强生长抑制作用，这意味着细胞内游离Ca²⁺浓度升高可能参与了这些作用。其他Na⁺-Ca²⁺交换阻滞剂如镍和苄amil，也显著增强了抗雌激素诱导的肿瘤细胞生长抑制作用。综上所述，这些药物对Na⁺-Ca²⁺交换机制的阻断可能导致细胞内Ca²⁺浓度升高的时间延长，进而导致肿瘤细胞生长抑制作用增强。这些结果表明，苄普地尔与抗雌激素药物联合治疗可能是脑肿瘤化疗的一种潜在策略。
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