海南哥纳香醇甲(GHM-10)对体外L1210细胞的抗肿瘤活性

用体外培养法研究GHM-10对L1210细胞生长的抑制作用和作用机制。结果表明,L1210细胞在用GHM-10处理1h,24h和7d后,IC₅₀依次为6.85,3.32和1.59μg·ml^-1,提示GHM-10有非时相特异性细胞毒药物的特性。在用GHM-10 1～2μg·ml^-1作用24h后,L1210细胞的增长率和有丝分裂指数下降,细胞核形态发生变化,但活细胞率仍保持在96%以上,提示GHM-10主要抑制细胞的增殖。用流式细胞计对L1210细胞进行细胞周期动力学的分析表明,GHM-10可在一定程度上阻断G₁期细胞向S期移行,还可增加L1210细胞的膜流动性。

Antitumor activity of howiinol (GHM-10) on L1210 cells in vitro]

Howiinol(GHM-10) is a new compound isolated from Goniothalamus howii. Previous studies showed that GHM-10 significantly inhibited the growth of cancer cells both in vitro and in vivo. In the present study, the characteristics of the inhibitory effect of GHM-10 on L1210 cells was investigated. The results showed that the IC50 of L1210 cells treated with GHM-10 for 1 h, 24 h, and 7 d was 6.85, 3.32 and 1.59 micrograms.ml-1, respectively. This outcome is in compliance with the hypothesis that GHM-10 is a cell cycle non-specific cytotoxic drug. When L1210 cells were treated with 1-2 micrograms.ml-1 of GHM-10 for 24 h, the growth rate and mitotic index were decreased and the morphology of cell nuclei changed, but the cell viability remained at the level of 96% or more, indicating that GHM-10 mainly inhibited cell proliferation. The cell cycle kinetics of L1210 cells were studied by using a flow cytometer. The results showed that the transition of cells from G1 phase to S phase was blocked to certain extent by the treatment of GHM-10 4 micrograms.ml-1 for 12 h. The fluidity of cell membrane was also increased when the L1210 cells were exposed to 2-3 micrograms.ml-1 of GHM-10 for 24 h.