异紫堇二酮体内外抗肿瘤活性研究

目的异紫堇二酮的体内外抗肿瘤活性及其作用机制的初步研究。方法通过异紫堇二酮对体外培养肿瘤细胞的生长抑制,体内荷S180瘤和荷H22瘤昆明种小鼠的肿瘤生长抑制、体重以及对小鼠免疫器官的影响(脾脏指数、胸腺指数),对其抗肿瘤活性进行综合评价,并通过流式细胞术检测异紫堇二酮作用下肺腺癌细胞(A549)的细胞凋亡及周期分布情况,初步探讨该化合物的抗肿瘤作用机制。结果异紫堇二酮对9种所选肿瘤细胞具有一定的生长抑制作用,IC50值在1.452×104～2.460×104 mol.L-1之间;流式细胞术检测结果显示异紫堇二酮可诱导A549细胞凋亡,使A549细胞阻滞于G0/G1期并随作用时间延长出现明显的凋亡峰;剂量为100和200 mg.kg-1.d-1时,异紫堇二酮对荷S180瘤和荷H22瘤小鼠的抑瘤率均大于40%,但剂量在200 mg.kg-1.d-1时,荷瘤小鼠的胸腺指数与脾脏指数相比较生理盐水组均有明显降低。结论异紫堇二酮具有一定的抗肿瘤活性,其主要是阻断肿瘤细胞由G0/G1期向S期转变来诱导肿瘤细胞死亡。

Antitumor activity of isocorydione in vitro and vivo

Aim To evaluate the antitumor activity and the mechanism of isocorydione in vitro and vivo assays.Methods Antitumor activity was comprehensively evaluated by the experiment about the growth inhibition of tumor cells in vitro with isocorydione;and the experiment about growth inhibitory of S180 tumor and H22 tumor bearing body on weight and immune organs(Spleen index,thymus index) of kunming mice.Moreover,the effect of mitotic cycle and apoptosis on lung cancer cells was determined,the anti-tumor mechanism of isocorydione was preliminarily studied.Results Isocorydione had a certain inhibitory on the growth of the nine common tumor cells we chose,the half inhibitory concentration(IC50) ranged from 1.452×104 mol·L-1 to 2.460×104 mol·L-1.The results of flow cytometry showed that isocorydione could induce apoptosis of A549 cell,and A549 cell could be arrested in G0/G1 phase.Meanwhile,it showed an obvious apoptotic peak when extending the working time.In animal experiments,when the dose of isocorydione was 100 mg·kg-1·d-1 and 200 mg·kg-1·d-1,the inhibitory rate of tumor was greater than 40% in both S180-bearing or H22-bearing mice.However,when the dose of isocorydione was higher than 200 mg·kg-1·d-1,the thymus index and spleen index both declined obviously compared with saline group.Conclusion Isocorydione has a certain degree of antitumor activity,and its inhibitory effect on tumor cells is performed by preventing the cell transition from G0/G1 phase to S phase to induce cells apoptosis.