Hait W N, Lazo J S
J Clin Oncol. 1986 Jun;4(6):994-1012. doi: 10.1200/JCO.1986.4.6.994.
Calmodulin is a ubiquitous, calcium-binding protein that is responsible for many of the intracellular actions of calcium. Recent evidence suggests that calmodulin may regulate cellular proliferation and that its function may be altered in malignancy. The discovery that drugs such as phenothiazines antagonize the action of calmodulin led to the study of these antagonists against tumor cells. It is now appreciated that calmodulin antagonists are cytotoxic, can restore the sensitivity of resistant cells to drugs such as doxorubicin and vincristine, and can augment the cytotoxicity of bleomycin. This report addresses the possibility of developing new forms of chemotherapeutic agents that work by disrupting the function of this intriguing molecule.
钙调蛋白是一种普遍存在的钙结合蛋白,它负责许多钙的细胞内作用。最近的证据表明,钙调蛋白可能调节细胞增殖,并且其功能在恶性肿瘤中可能会发生改变。诸如吩噻嗪类药物能拮抗钙调蛋白作用这一发现,引发了对这些拮抗剂针对肿瘤细胞的研究。现在人们认识到,钙调蛋白拮抗剂具有细胞毒性,能恢复耐药细胞对阿霉素和长春新碱等药物的敏感性,还能增强博来霉素的细胞毒性。本报告探讨了开发通过破坏这种有趣分子的功能来发挥作用的新型化疗药物的可能性。