Santamarin的抗肿瘤活性及对DNA拓扑异构酶的影响

目的研究Santamarin的体内外抗肿瘤活性及对DNA拓扑异构酶(TOPO)活性的影响。方法以7株人肿瘤细胞株为模型,采用改良MTT法检测Santamarin对肿瘤细胞增殖的影响;以小鼠移植性肉瘤S180和小鼠移植性肝癌H22为模型,检测Santamarin对在体肿瘤生长的影响;以pBR322 DNA为底物,采用琼脂糖凝胶电泳检测Santamarin对TOPO介导的pBR322 DNA解旋反应的影响,以及对pBR322 DNA是否具有直接断裂作用。结果Santamarin对7株人肿瘤细胞株的半数抑制浓度(IC50)在0.99~3.61mg·L-1之间;Santamarin30、90和270mg·kg-1剂量对S180生长的抑制率分别为51.44%、63.60%和56.37%;对H22生长的抑制率分别为40.77%、39.47%和46.73%。Santamarin在2g·L-1时完全抑制TOPOI、Ⅱ的活性,但对DNA无直接断裂作用。结论Santamarin具有较为明显的体内外抗肿瘤活性,对DNA TOPO活性的抑制可能是其作用机制之一。

Antitumor activity of santamarin and its effect on topoisomerase

Aim To investigate the antitumor effect of santamarin isolated from Cyathocline purpurea and its mechanism of action.Methods The cytotoxicity of santamarin on seven human tumor cell lines were detected by modified MTT assay in vitro, and the in vivo antitumor effects on the sarcoma 180(S180)and hepatoma 22(H22)bearing in mice were evaluated by tumor weight. The effects of santamarin on topoisomerase(topo)-mediated pBR322 DNA cleavage and on direct pBR322 DNA break were measured by using agarose gel electrophoresis.Results Santamarin showed a definite cytotoxicity to seven tumor cell lines with IC50 in the range of 0.99～3.61 mg·L-1.Santamarin at the dose of 30、90、270 mg·kg-1administrated by oral route inhibited significantly the growth of S180 and H22 bearing in mice, the inhibitory rate were 51.44%、63.60%、56.37% and 40.77%、39.47%、46.73% respectively.At the concentration of 2 g·L-1,santamarin completely inhibited the pBR322 DNA cleavage mediated byTOPO I and Ⅱ,but it had no effect on direct pBR322 DNA break.Conclusions Santamarin has significant antitumor effect in vitro and in vivo, and has moderate inhibitory effect on topoisomerases, which may be the main target of antitumor activity of santamarin.