自由基在鬼臼酰肼哌啶腙氮氧自由基抗肿瘤及毒性中的作用(英文)

探索鬼臼酰肼哌啶腙氮氧自由基（ＧＰ－１）中自由基对其抗肿瘤作用及毒性的影响．方法：采用小鼠移植肿瘤及体外培养的肿瘤细胞系，检测ＧＰ－１及其自由基还原物ＧＰ－１－Ｈ的体内外抗肿瘤作用，毒性及对细胞周期，有丝分裂指数和小鼠免疫功能的影响．结果： ＧＰ－１　１／６， １／１２ ＬＤ５０给药１０ｄ，对小鼠Ｌｅｗｉｓ肺癌， Ｓ１８０， Ｐ３８８和 ＨｅＰＳ生长的抑制作用，在体外对ＳＧＣ－７９０１细胞增殖和Ｌ１２１０细胞ＤＮＡ合成的抑制作用均比ＧＰ－１－Ｈ强．其对Ｌ１２１０细胞作用环节在细胞周期的Ｍ期之后．ＧＰ－１－Ｈ对细胞周期的影响与ＧＰ－１相似，但作用较弱．结论：ＧＰ－１中的自由基在增强其抗肿瘤作用中起着重要作用。

Action of free radical in podophyllic acid piperindyl hydrazone nitroxide radical on its antitumor activity and toxicity

AIM: To study the action of free radical in the spinlabeled podophyllotoxin derivative, podophyllic acid piperindyl hydrazone nitroxide radical (GP-1) on its antitumor activity and toxicity, by comparison with those of its free radical reduced product, podophyllic acid piperindyl hydrazone (GP-1-H). METHODS: After treatment with GP-1 and GP-1-H, the inhibitory effects on the growth of mouse transplantable tumors were determined; determined; MTT formation, [3H] deoxythymidine ([3H]TdR) incorporation, cell cycle progression, and mitotic index of SGC-7901 or L1210 cells were measured; the acute toxicity and immune function of mice were assayed. RESULTS: At doses of 1/6 and 1/12 LD50, the inhibitory rates against Lewis lung carcinoma were 60.3% and 42.1% (GP-1), 38.9 % and 10.3% (GP-1-H), respectively; more effective antitumor activity of GP-1 against P388, HePS, and S-18O than that of GP-1-H were found. In vitro, GP-1 exhibited more powerful inhibitory effects on the proliferation and DNA synthesis of SGC-7901 and L1210 cells than GP-1-H. GP-1 and GP-1-H arrested the L1210 cells at G2/M phase with a corresponding decrease of the cells in G1 phase, and increased the mitotic index of the cells; but the effects of GP-1-H were weaker than those of GP-1. After treatment with doses of 1/4 and 1/8 LD50 for 5 d, no significant difference on immune function of mice between GP-1 and GP-1-H was found. CONCLUSION: GP-1 had more powerful antitumor activities than GP-1-H. The free radical in the spin-labeled podophyllotoxin derivative, GP-1, played an role in its antitumor activity.