吗丙嗪和阿霉素合用对肿瘤细胞周期及DNA合成的影响

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。

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

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.