4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4′-去甲表鬼臼毒对L1210细胞系增殖、克隆形成和DNA合成的影响

新合成的鬼臼毒自旋标记衍生物4-(4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基)-4′-去甲表鬼臼毒(GP-7)显著抑制体外培养的L1210细胞生长。抑制作用和浓度及处理时间正相关,作用特点和鬼臼乙叉甙(VP-16)相似,24,48hIC_(50)分别为1.51和0.13μmol/L。GP-7和VP-16对L1210细胞软琼脂克隆形成均有抑制作用,且有浓度依赖性,IC_(50)分别为3.29和2.82μmol/L。GP-70.08～100μmol/L对L1210细胞DNA合成抑制率为18.4～80.7％。本文结果表明GP-7体外抗肿瘤作用与VP-16相似。

Effects of 4- [4"-(2",2",6",6"-tetramethyl-l"-piperidinyloxy)amino] -4'-demethylepipodophyllotoxin on the proliferation,clonal formation and DNA synthesis of L1210 cells in vitro

The effects of a new podophyllotoxin spin-labeled derivative, 4- 4"-(2", 2", 6", 6"-tetra methyl-1"-piperidinyloxy) amino] -4'-demethyle pipodophyllotoxin (GP-7) on the proliferation, clonal formation and incorporation of 3H] TdR into DNA of L1210 cells in vitro were observed compared with VP-16. It was found that the proliferation of L1210 cells was markedly inhibited and the inhibition rate had a positive interrelationship with the concentration and exposure time. At the concentration of 0.08-100 μmol/L, inhibition rate was 18.4-80.7% and IC50 was 1.51μmol/ L. After exposure of the cells to GP-7 5 μmol / L for 6, 12, 24 and 48 h, the inhibition rates were 21.7, 42.2, 60.6 and 81.2% respectively. Thebehavior of GP-7 on the proliferation of L1210 cells was similar to that of VP-16. The clonal formation of L1210 cells was inhibited by GP-7 and VP-16 with the IC50 of 3.29 and 3.82 μmol / L respectively. After exposure to 0.08-100 μmol / L GP-7 for 24 h, the inhibition rate of the incorporation of 3H] TdR into DNA of L1210 cells was 21.4-81.2 %.These results suggested that GP-7 had a similar remarkable antitumor activity in vitro as VP-16.