喜树碱多相脂质体对肿瘤细胞动力学及分子药理学研究

喜树碱多相脂质体对肝癌细胞具有抑制增殖的效应,明显损伤S期细胞,对于G_0期细胞亦有轻度损伤,G_2期细胞进入M期也受到一定抑制。10mg/kg静注后肝癌组织中cAMP水平明显增加,而肝癌组织中DNA和蛋白质含量显著下降,cAMP与cGMP比值大幅度提高。喜树碱多相脂质体对肝癌细胞DNA合成的最高抑制率为73.7%,后作用约4小时,对癌细胞RNA合成的抑制率达82.9%。

STUDIES NO THE CYTOKINETICS OF CANCER CELLS AND MOLECULAR PHARMACOLOGY OF POLYPHASE LIPOSOME OF CAMPTOTHECIN

The effects of Polyphase Liposome of Camptothecin Sodium (PL-CS) on the life of Hepa-toma cells in mice were studied by autoradiographic method. The experimental results showedthat cells in S phase might be killed by PL-CS. PL-CS prevented strongly the cell progressionfrom S phase into M phase. Five hours after the administration of PL-CS the damaged cells in Go phase were about9.5%. PL-CS could induce an accumulation of cAMP in hepatoma at the i.v. dose of 10mg/kg, which produced an inhibition on tumor growth. cAMP concentration was related to DNAcontents in the hepatcma cells. PL-CS produced a remarkable inhibition on DNA and Proteincontents and increased cAMP concentration in the tumor cells. The ratio of cAMP/cGMP inhepatoma tissue was increased significantly.The effect of PL-CS on the formation of DNA wasstudied using a method of incorporating ~3H-TdR into hepatoma cells in mice. The maximumintensity of inhibition was 73.7%, which was 61.0% that of cytosine arabinoside. Maximaminhibition was observed 2 hour after drug administration and disappeared 4 hours later. Thesynthesis of RNA in hepatoma cells was inhibited by PL-CS at a concentration of 1.0mg/ml,the maximum intensity of inhibition being 82.9%.