Hall T J, Jeker H, Schaueblin M
Ciba-Geigy Ltd., Research Department, Basel, Switzerland.
Calcif Tissue Int. 1995 Dec;57(6):463-5. doi: 10.1007/BF00301951.
We have examined the effect of the anti-tumor compound taxol, on osteoclastic bone resorption. In the bone slice assay, taxol (0.1-0.001 microM) dose-dependently inhibited bone resorption with an IC50 of 0.08 microM. Osteoclast survival on bone slices was unaffected by 0.01-1 microM taxol, but 10 microM was cytotoxic. Taxol (1 microM) also inhibited osteoclast spreading (45%) on fibronectin-coated slides. The antiproliferative effects of taxol are due to its unique ability to stabilize microtubules. Primary osteoclasts are nonproliferating end cells, so taxol probably inhibits bone resorption by interfering with other microtubule-dependent functions such as cell polarization, motility or vesicle exocytosis. Since these inhibitory effects on osteoclasts in vitro are seen with therapeutically relevant concentrations, taxol therapy may have beneficial side-effects e.g. inhibition of hypercalcemia and bone metastases.
我们研究了抗肿瘤化合物紫杉醇对破骨细胞骨吸收的影响。在骨片试验中，紫杉醇（0.1 - 0.001微摩尔）呈剂量依赖性抑制骨吸收，IC50为0.08微摩尔。0.01 - 1微摩尔的紫杉醇对骨片上破骨细胞的存活没有影响，但10微摩尔具有细胞毒性。紫杉醇（1微摩尔）还抑制破骨细胞在纤连蛋白包被载玻片上的铺展（45%）。紫杉醇的抗增殖作用归因于其稳定微管的独特能力。原代破骨细胞是不增殖的终末细胞，因此紫杉醇可能通过干扰其他微管依赖性功能（如细胞极化、运动或囊泡胞吐作用）来抑制骨吸收。由于在治疗相关浓度下可观察到对破骨细胞的这些抑制作用，紫杉醇治疗可能具有有益的副作用，例如抑制高钙血症和骨转移。
