表没食子儿茶素没食子酸酯增强阿糖胞苷对HL-60细胞的抗肿瘤活性

 目的：研究表没食子儿茶素没食子酸酯（EGCG）增强阿糖胞苷（AraC）对人白血病HL-60细胞的抗肿瘤活性。方法：采用生长曲线法、MTT法测定AraC合并应用EGCG前后对HL-60细胞的增殖抑制作用；以对消实验研究EGCG能否逆转脱氧胞苷（dCdR）的补救作用；以流式细胞光度仪分析联合用药前后对细胞周期和细胞凋亡的影响。结果：合并EGCG能增强AraC对HL-60细胞的增殖抑制作用，倍增时间从48 h延长到70 h，生长饱和密度从5.78减少到对5.54；MTT法表明合并EGCG后，AraC对HL-60细胞的IC₅₀从(0.08±0.07) μg·ml^-1减少到0.024±0.026 μg·ml^-1(P＜0.05)；对消实验表明单用AraC的IC₅₀为6.25 ng·ml^-1,加上dCdR后IC50为5.24 μg·ml^-1,而在给予EGCG后IC₅₀减少到1.17 μg·ml^-1。细胞周期研究结果表明AraC可使HL-60细胞阻滞于G₁期，S期细胞减少，低浓度的EGCG对细胞周期几无影响，但增强了AraC的细胞周期阻滞作用及细胞凋亡。结论：AraC合并应用EGCG可增强对人白血病HL-60细胞的抗肿瘤活性。

Potentiation of antitumor effect induced by cytosine arabinoside with (-)-epigallocatechin-3-gallate in HL-60 cells

OBJECTIVE To study the potentiation of antitumor effect induced by cytosine arabinoside (AraC) with (-)-epigallocatechin-3-gallate (EGCG). METHODS Growth curve method and MTT method were used to measure the antitumor effect induced by AraC alone and in combination with EGCG in HL-60 cell line. Nullification assay was used to examine whether EGCG nullify the rescue effect of deoxycytidine (dCdR) to AraC. Flow cytometry was used to study the effect on cell cycle by AraC alone and in combination with EGCG. RESULTS The HL-60 cell proliferation inhibition induced by AraC was enhanced by EGCG, with multiplication time prolonging from 48h to 72h and growth saturation density decreasing from 5.78 to 5.54. The MTT results indicated that IC₅₀ was decreased from 0.083±0.073 μg·mL^-1 (AraC alone) to 0.024±0.026 μg·ml^-1(P＜0.05) (in combination with EGCG); Nullification assay indicated that IC₅₀ was 6.25 ng/ml (AraC alone), increased to 5.24 μg·mL^-1 when rescued with dCdR, and finally decreased to 1.17 μg·ml when addition with EGCG; Cell cycle analysis indicated that AraC blocked HL-60 cells in G₁, inhibited cells in S, while EGCG had no effect on cell cycle at the current concentration, but could enhance the cell arrest by AraC. CONCLUSIONS The combination with EGCG could enhance the antitumor effect induced by AraC.