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研究香兰素衍生物中的6-溴异香兰素(6-溴-5-羟基-4-甲氧基苯甲醛,BVAN08)对人宫颈癌上皮(HeLa)细胞纺锤体结构、有丝分裂的影响,及杀死癌细胞的相关机制,为开发新的抗癌药物提供理论依据。研究发现BVAN08对体外培养的人HeLa细胞具有剂量依赖性致死效应。通过抗α-微管蛋白抗体和抗β-微管蛋白抗体免疫荧光标记和激光共聚焦显微镜观察发现其机制是:BVAN08对细胞纺锤体结构造成破坏,诱发产生大量的多中心体细胞,使细胞阻滞在有丝分裂期。异常多极纺锤体细胞的百分率与BVAN08呈浓度依赖效应关系。荧光染料Hoechst33258染色观察到多微核或细胞核割裂和染色质凝集现象,也证实BVAN08诱发Hela细胞有丝分裂灾变死亡。同时免疫印迹实验还发现,BVAN08可导致细胞周期转录调节因子FoxM1(Forkhead box)及其下游靶分子CyclinB1的降解,参与有丝分裂的FoxM1蛋白失活,这表明BVAN08通过抑制FoxM1蛋白的表达是导致细胞纺锤体装配异常、细胞发生有丝分裂灾变死亡的分子机制之一。研究结果提示BVAN08诱发Hela细胞新的死亡方式,具有被开发为新型抗癌药物的潜力。
To investigate the effect of 6-bromo-5-hydroxy-4-methoxybenzaldehyde (BVAN08) in vanillin derivatives on the spindle structure and mitosis of human cervical cancer cell line HeLa, And kill the related mechanisms of cancer cells, to provide a theoretical basis for the development of new anti-cancer drugs. The study found that BVAN08 on human HeLa cells cultured in a dose-dependent lethal effect. By anti-α-tubulin antibody and anti-β-tubulin antibody immunofluorescence labeling and confocal laser scanning microscopy showed that the mechanism is: BVAN08 on the spindle structure of the cell damage, induced a large number of polycentric somatic cells, the cells Blocking during mitosis. The percentage of abnormal multipolar spindle cells was correlated with BVAN08 in a concentration-dependent manner. Fluorescent dye Hoechst33258 staining observed micronucleus or nuclear fragmentation and chromatin agglutination phenomenon, also confirmed BVAN08 induced Hela cell mitotic death. Western blotting also showed that BVAN08 could lead to the degradation of FoxM1 (Forkhead box) and its downstream target molecule CyclinB1, which is involved in the deactivation of mitotic FoxM1 protein. This indicates that BVAN08 can inhibit the expression of FoxM1 protein by inducing cell spindle Body assembly abnormalities, mitochondrial cell death occurs one of the molecular mechanisms. The results suggest that BVAN08 induced Hela cells a new way of death, has been developed as a new type of anticancer drug potential.