5-氮杂胞苷与盐酸洛拉曲克体外联合用药的抗癌增效作用观察

目的 通过在体外分别对DNA甲基化转移酶（DNA methy ltransferase，DNMT）抑制剂5-氮杂胞苷（5-azacytidine，5-aza-C）和新型脂溶性胸苷酸合成酶抑制剂盐酸洛拉曲克（nolatrexed dihydrochloride，Nolatrexed）联合用药于人大肠癌细胞LoVo和人肝癌细胞Hep3B 的相互作用的性质观察，探讨DNMT抑制剂和胸苷酸合成酶抑制剂联合用药的可能性．方法 使用MTT法测定5-aza-C和Nolatrexed单独用药或联合用药的抗癌活性，用抑制浓度的分数之和（a sum of fractio nal inhibitory concentration，SFIC）值及等效剂量分析方法（Isob010gram）评价5-aza-C和Nolatrexed联合用药的作用性质．结果 在5-aza-C和Nolatrexed联合用药时其SFIC值均小于或等于l，由此得到的等效剂量曲线图形表现为凹形．结论 5-aza-C和Nolatrexed体外联合用药抗癌相互作用性质为明显的增效作用，DNMT抑制剂和胸苷酸合成酶抑制剂联合用药达到抗癌增效作用是可能的．

Synergistic anticancer wffect of 5-azacytidine combined with nolatrexed dihydrochloride in vitro

Objective To study the interaction between 5-azacytidine (5-aza-C) and nolatrexed dihydrochloride(Nolatrexed )against LoVo cell and Hep3B cell in vitro,and explore the possibility of combining DNA methyltransferase inhibitors with thymidylate synthase inhibitors. Methods Anticancer activities of 5-aza-C and Nolatrexed alone and combination of the two drugs were determined by tetrazolium (MTT) method. The interaction between 5-aza-C and Nolatrexed was evaluated by both a value of a sum of fractional inhibitory concentration (SFIC) and an isobologram method. Result All the SFIC values of the combination between SPB and Nolatrexed were less than or equal to 1.0. And the shapes of isobolic curves obtained from the combination were concave. Conclusion The interaction between 5-aza-C and Nolatrexed against human cancer cells can get markedly synergistic effect, suggesting the potential synergistic anticancer effects of combining DNA methyltransferase inhibitors with thymidylate synthase inhibitors in clinical application.