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本实验室以前的工作表明AT_(1420)具有显著抗瘤活性而无蓄积毒性。本文进一步表明:AT_(1420)主要抑制指数生长期的EAC细胞;在体外对培养中的HeLa细胞有直接细胞毒作用,100μg/ml浓度对~3H-TdR参入的抑制率43—55％.50μg/ml抑制率23—26％,25μg/ml抑制率为16％。采用显微分光光度计测定单个细胞DNA含量,并用电脑分析数据,对EAC细胞增殖周期动力学研究表明:用药后4小时即出现G_1期细胞堆积,进入S期受阻。用药后24小时仍有大量细胞堆积于G_1期,并出现相当部分低DNA含量的细胞。提示临床应用AT_(1420)时不宜与S期特异性药物(如MTX AraC等)同时使用以免产生自限作用而降低疗效。
Previous work in our laboratory showed that AT_(1420) has significant antitumor activity without accumulation of toxicity. This article further shows that AT 1420 mainly inhibits exponentially growing EAC cells and has a direct cytotoxic effect on HeLa cells in culture. The inhibitory rate of 100 μg/ml concentration to ~3H-TdR incorporation is 43-55%, 50 μg. The inhibition rate of /ml was 23-26%, and the inhibition rate of 25 μg/ml was 16%. Using a microscopic spectrophotometer to determine the DNA content of individual cells and analyzing the data with a computer, the kinetics of the proliferation cycle of EAC cells showed that cells in the G1 phase appeared to accumulate at 4 hours after administration and were blocked in the S phase. A large number of cells still accumulated in the G1 phase 24 hours after administration, and a considerable part of cells with low DNA content appeared. It is suggested that when applying AT_(1420) clinically, it should not be used together with S-phase specific drugs (such as MTX AraC, etc.) to avoid self-limiting effects and reduce the efficacy.