B 细胞低度非霍奇金淋巴瘤中钙通道阻滞剂与细胞毒性化疗的体外试验
In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell low-grade non-Hodgkin's lymphoma.
作者信息
Shamash J, Salam A H, Davies D C, Williams A, Joel S, Lister T A
机构信息
ICRF Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
出版信息
Br J Cancer. 1998 May;77(10):1598-603. doi: 10.1038/bjc.1998.262.
The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azumolene for the treatment of low-grade non-Hodgkin's lymphoma is warranted.
钙通量形成了一个重要的细胞内信使系统。bcl-2癌蛋白被认为通过抑制细胞凋亡使细胞对包括细胞毒性药物在内的多种损伤产生抗性，而细胞凋亡似乎涉及细胞内钙的重新分配。在细胞培养中，使用一种转化的滤泡中心淋巴瘤细胞系和淋巴瘤细胞的原代培养物，以一种产生与体内恶性肿瘤生长模式极为相似的方式，研究了三种影响钙途径并可能影响这种重新分配的药物，即丹曲林、阿祖莫林（一种水溶性丹曲林类似物）和尼莫地平。在这两种体系中，丹曲林和阿祖莫林都是有效的细胞死亡诱导剂，与正常对照相比，可使活细胞数量减少70%-90%。相比之下，尼莫地平似乎没有显著作用。在体外环境中获得的这些结果表明，有必要对丹曲林和阿祖莫林用于治疗低度非霍奇金淋巴瘤进行进一步评估。
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