吉西他滨联合培美曲塞不同序贯用药时序对HUT-78细胞增殖及凋亡的影响

Effect of gemcitabine combined with pemetrexed on proliferation and apoptosis of HUT-78 cell

目的观察吉西他滨与培美曲塞单药及不同时序联合用药方案对人皮肤T细胞淋巴瘤HUT-78细胞增殖及凋亡的影响。方法采用体外培养技术,应用不同浓度的吉西他滨及培美曲塞处理HUT 78细胞,CCK-8法确定两药的IC50值,后应用CCK-8法及Annexin V-FITC法检测两药不同顺序联合应用对HUT-78细胞增殖及凋亡的影响。结果吉西他滨及培美曲塞单药对HUT-78细胞的增殖的抑制具有时间依赖性及浓度依赖性,吉西他滨的IC50值为(7.50±0.71)×10-3μg/ml,培美曲塞的IC50值为(1.72±0.52)μg/ml。不同顺序药物联合应用效果不同,先用培美曲塞后用吉西他滨及同时应用具有协同作用,抑制率及凋亡率均较各单药组高,而先用吉西他滨后用培美曲塞则无协同作用。结论吉西他滨与培美曲塞单药以及不同时序联合应用均可抑制HUT-78的增殖促进凋亡,作用大小与应用时序有关,先用培美曲塞再用吉西他滨的作用最强。

Objective To investigate the effect of concentrations of gemcitabine and pemetrexed alone and in combination on proliferation and apoptosis of cutaneous T-cell lymphoma cell line HUT-78 in vitro.Methods HUT-78 cell was cultured in vitro,HUT 78 cell was treated with different concentrations of gemcitabine and pemetrexed.The IC5o of the two drugs were detected by CCK-8 method,then given the concentrations of gemcitabine and pemetrexed in combination with different sequence.The growth inhibition rate was detected by CCK8 method,and the apoptosis rate was analyzed by Annexin V-FITC method.Results Gemcitabine or pemetrexed significantly inhibited the growth of HUT 78 cell in a dose andtime dependent manner.The IC50 of gemcitabine was （7.50 ± 0.71） × 10-3 μg/ml,the IC50 of pemetrexed was （1.72 ± 0.52） μg/ml.The effect of combination was varied with the order of the drug delivery.Synergistic effect was found in the administration of gemcitabine after pemetrexed and administration of simultaneous drug,inhibition rate and apoptosis rate were higher than those of each mono-drug treated group,the group of pemetrexed after gemcitabine had no synergistic effect.Conclusions Both monodrug program and combined scheme could inhibit proliferation and promote apoptosis of HUT-78 cell,and the effect of combination varied with the order of the drug delivery the sequential regimen of pemetrexed followed by gemcitabine might has the strongest effect.