摘要
Ｔｏｐｏｔｅｃａｎ（ＴＰＴ）是类似天然抗癌药物喜树碱的半合成新药．为了阐明ＴＰＴ对拓扑异构酶的毒性作用，将癌细胞系ＳＵＤ４及ＤＯＨＨ２培养在不同浓度ＴＰＴ的培养基中，分别在培养８ｈ、１８ｈ后取样进行测试．结果表明：ＴＰＴ不仅作用于拓扑酶Ⅰ，也作用于拓扑酶Ⅱ，尽管对酶Ⅱ的影响非常小．应用新的流体细胞测量仪（ＦＡＣＳ－Ｖａｎｔａｇｅ）及免疫分析法对细胞培养时间、ＴＰＴ的浓度与拓扑酶中毒程度的动力学关系进行了研究．上述研究显示ＴＰＴ能影响拓扑异构酶Ⅱ（新观点），同时强调在抗癌化学治疗中应结合使用酶Ⅰ及酶Ⅱ抑制剂．
Topotecan(TPT)is a semisynthetic analogue of the natural product
camptothecin that exerts antineoplastic activity.To elucidate the cytotoxic effect of TPT on
topoisomerase (Topo ⅠorⅡ)in this study.Cancer cell line cells (SUD4/DOHH2)were incubated
for 8 h or 18 h with TPT at various concentration.TPT was detected to have cytotoxic effect not
only on Topo Ⅰbut also on Topo Ⅱ,although it is much less on Topo Ⅱ than on Topo Ⅰ.The
dynamic relationship between cytotoxic effect and incubated time with TPT was investigated by
flow cytometry and immunological analysis.These results put out an new view that TPT inhibits
Topo Ⅱ and emphasised the critical role of schedule dependency to optimise the effectiveness
of combination chemotherapy with Topo Ⅰ and Topo Ⅱinhibitor.
出处
《生命科学研究》
CAS
CSCD
1999年第2期110-117,共8页
Life Science Research
