吗丙嗪和阿霉素合用对肿瘤细胞周期及DNA合成的影响  

Effect of probimane and doxorubicin in combination on DNA synthese and cell cycle of tumor cells

作　　者：张予[1] 刘健[1] 王筠[1] 叶启霞[1] 张覃沐[1] 

机构地区：[1]河南省医学科学研究所药理室

出　　处：《中国药理学通报》1997年第6期535-537,共3页Chinese Pharmacological Bulletin

基　　金：河南省自然科学基金

摘　　要：目的：观察吗丙嗪（Ｐｒｏ）和阿霉素（Ｄｏｘ）合用对肿瘤细胞周期及ＤＮＡ合成的影响，以探讨吗丙嗪增强阿霉素抗肿瘤作用之机制。方法：采用拒染法观察Ｐｒｏ，Ｄｏｘ和Ｐｒｏ＋Ｄｏｘ对小鼠体外艾氏腹水癌细胞（ＥＡＣ）的杀伤作用；采用标记前体物参入法和显微分光光度术观察两药合用对ＥＡＣ细胞周期及ＤＮＡ合成的影响。结果：Ｐｒｏ２１．４６，４２．９２和６４．３８μｍｏｌ·Ｌ－１增强Ｄｏｘ对ＥＡＣ细胞的杀伤作用；Ｐｒｏ（２１４．５９μｍｏｌ·Ｌ－１）和Ｄｏｘ（１８．０２μｍｏｌ·Ｌ－１）合用对ＥＡＣ细胞ＤＮＡ合成有明显的抑制作用；用药后４～８ｈＧ１期细胞增加，ＤＮＡ直方图左移，各用药组细胞分裂指数无明显差异。结论：Ｐｒｏ可增强Ｄｏｘ的抗肿瘤作用，其机理可能与Ｐｒｏ加强Ｄｏｘ对ＤＮＡ合成的抑制及对Ｇ１期细胞累积作用增强有关。AIM: To study the mechanism of synergistic effect of probimane (Pro) on doxorubicin (Dox) cytotoxicity. METHODS: Using typen blue exclusion method, the effect of probimane on Dox cytotoxicity was studied. By the technique of tritiumlabeled TdR uptake and microphotometry, the effect of the combination of Pro with Dox on DNA synthesis and cytokinetic changes of ehrlich ascites carcinoma (EAC) cells in vitro were studied. RESULTS: Pro 2146,4292 and 6438 μmol·L-1 potentiated cytotoxicity of Dox in EAC cells. The DNA synthesis was markedly inhibited by combination of Pro (21459 μmol·L-1) and Dox (1802 μmol·L-1) in vitro as compared to that by each drug using alone. The cytokinetic changes of EAC cells on combination of Pro with Dox were as follows: 4 to 8 h after treatment of the drugs, an enrichment of cells in G1 phase and the DNA histogram shifted to the left were found. There was no change in mitotic index in each group. CONCLUSIONS: The results suggested that the combination of Pro and Dox could synergistically affect the tumor cells in S and G2 phase.

关 键 词：吗丙嗪 阿霉素 联合用药 肿瘤细胞周期 DNA合成 

分 类 号：R979.1[医药卫生—药品]