钩吻生物碱化合物抗肿瘤效应及其诱导凋亡作用

目的研究钩吻生物碱化合物抗肿瘤效应及其诱导凋亡作用。方法①在小鼠H22肝癌细胞小鼠移植性肿瘤模型上观察钩吻生物碱化合物对H22小鼠实体瘤的抑制作用；②AO／EB荧光染色法观察凋亡细胞的形态学变化；流式细胞仪PI染色检测细胞周期变化及凋亡率。结果腹腔注射钩吻素子对H22小鼠实体瘤的抑瘤率为40．29％、36．57％、22．89％；钩吻素甲对小鼠H22实体瘤的生长具有一定的抑制作用，抑瘤率为28．91％、16．85％、9．68％；但1-甲氧基钩吻碱小鼠H22实体瘤没有明显的抑制作用。钩吻素子可诱导SW480细胞发生凋亡形态学改变．并且可使SW480细胞周期阻滞于s期，阻止细胞从s期至G2期转移，从而诱导其凋亡。结论钩吻生物碱化合物特别是钩吻素子具有较强的抗肿瘤活性并具有一定的构效关系，钩吻索子的抗肿瘤作用机制可能与阻滞肿瘤细胞周期和促进肿瘤细胞凋亡作用有关。

Antitumor Effects and Mechanisms of Alkaloidal Compounds from Gelse-mium Elegans Benth

OBJECTIVE To investigate the antitumor effect and mechanisms of alkaloidal compounds from Gel- semium elegans Benth. METHODS （①）The antitumor activity of alkaloid compounds were evaluated in the kunming mice bearing H22 hepatoma. （②）EB/AO double staining and The flow cytometry （FCM） were used to investigate ap- optosis ceils. RESULTS Koumine significantly inhibited in a dose-dependent manner, the inhibitory rates at dose the growth of mice implanted solid tumor of H22 hepatoma of4mg · kg-1,2mg · kg-1 ,1mg· kg-1 were 40.29%36.57% and 22. 89% respectively;Gelsemine could inhibite H22 tumor in a dose-dependent manner and the inhibi- tory rates at dose of 4mg · kg- i was 28.91% but Gelsevirine showed no significant inhibitory effect on H22 ;2. Using flow cytometry suggested that koumine inhibited cell growth by specific blocking of the progression of cells through S- phase of the cell cycle and inducing apoptosis of tumor cells. CONCLUSION The anticancer effects of alkaloidal compounds from Gelsemium elegans Benth indicated that it has sufficient potential investigation. Moreover,inducing cell cycle arrest and leading to tumor ceils apoptosis might be mechanisms involved in the anticancer activity. to warrant further one of the possible