Binet S, Fellous A, Lataste H, Krikorian A, Couzinier J P, Meininger V
Laboratoire d'Anatomie, Faculté de Médecine, Paris, France.
Semin Oncol. 1989 Apr;16(2 Suppl 4):5-8.
Preliminary clinical studies demonstrated that 5' nor-anhydro-vinblastine, Navelbine (NVB) has a broader antitumor activity and fewer neurotoxic effects than vinblastine or vincristine. The tectal plate anlage of mouse embryos at the earliest stages of neuronal differentiation were used to analyze and compare the effect of NVB, vincristine and vinblastine on axonal and mitotic microtubules after culture of post-implantation embryos in a medium containing the agent. All drugs are active on mitotic microtubules at the same concentration (0.1 mumol/L), inducing a depolymerization of microtubules and a blockade of cells at metaphase. At higher concentrations. NVB is the only one of the three drugs that induces a blockade of the cells at prophase. A depolymerization of axonal microtubules occurs at higher concentrations with NVB than with the two other vinca alkaloids. These results demonstrate that NVB is as active on mitotic microtubules and less active on axonal microtubules than vincristine and vinblastine. These findings can be related to the potent antitumor effect of the drug with minor neurotoxicity.
初步临床研究表明,5' 去甲 - 脱水长春碱,即诺维本(NVB),与长春碱或长春新碱相比,具有更广泛的抗肿瘤活性且神经毒性作用更少。在神经元分化的最早阶段,使用小鼠胚胎的视顶板原基,在含有该药物的培养基中培养植入后胚胎后,分析并比较NVB、长春新碱和长春碱对轴突微管和有丝分裂微管的影响。所有药物在相同浓度(0.1 μmol/L)下对有丝分裂微管均有活性,诱导微管解聚并使细胞在中期阻滞。在更高浓度下,NVB是这三种药物中唯一能使细胞在前期阻滞的药物。与其他两种长春花生物碱相比,NVB在更高浓度下会导致轴突微管解聚。这些结果表明,与长春新碱和长春碱相比,NVB对有丝分裂微管的活性相同,但对轴突微管的活性较低。这些发现可能与该药物强大的抗肿瘤作用及较小的神经毒性有关。