异紫堇二酮体内外抗肿瘤活性研究

Antitumor activity of isocorydione in vitro and vivo

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。

Aim To evaluate the antitumor activity and the mechanism of isoeorydione in vitro and vivo assays. Methods Antitumor activity was comprehensively e- valuated by the experiment about the growth inhibition of tumor cells in vitro with isoeorydione; and the exper- iment about growth inhibitory of S180 tumor and H22 tumor bearing body on weight and immune organs （Spleen index, thymus index） of kunming mice. Mo- reover, the effect of mitotic cycle and apoptosis on lung cancer cells was determined, the anti-tumor mecha- nism of isocorydione was preliminarily studied. Results Isocorydione had a certain inhibitory on the growth of the nine common tumor cells we chose, the half inhibi- tory concentration （ IC50 ） ranged from 1. 452× 10^4 mol . L-1 to 2. 460 ×10^4mol.L-1. The results of flow cytometry showed that isocorydione could induce apop-tosis of A549 cell, and A549 cell could be arrested in G0/G1 phase. Meanwhile, it showed an obvious apop- totic peak when extending the working time. In animal experiments, when the dose of isoeorydione was 100 mg- kg-1 . d-X and 200 mg- kg-1 .d-1, the inhibi- tory rate of tumor was greater than 40% in both S180- beating or H22-bearing mice. However, when the dose of isocorydione was higher than 200 mg .kg- . d-1, the thymus index and spleen index both declined obvi- ously compared with saline group. Conclusion Isoc- orydione has a certain degree of antitumor activity, and its inhibitory effect on tumor cells is performed by pre- venting the cell transition from G0/G1 phase to S phase to induce cells apoptosis.