羧胺三唑与SAHA联合用药抑制Lewis肺癌细胞的体内外研究

In vitro and in vivo study of the inhibitory effect of the combination of CAI and SAHA on Lewis lung carcinoma cells

目的研究羧胺三唑(CAI)与组蛋白去乙酰化酶抑制剂辛二酰苯胺异羟肟酸(SAHA)联合用药对Lewis肺癌细胞的抑制作用,对比联合用药与单药使用的药效差异。方法采用SRB法检测体外培养的Lewis肺癌细胞系在单独使用CAI或SAHA以及联合用药时的细胞活力变化;建立C57小鼠Lewis肺癌细胞皮下移植瘤模型,随机分为4组:溶剂对照组、CAI组、SAHA组、CAI+SAHA联合治疗组,连续给药25天,观察各组小鼠体质量变化、肿瘤体积、肿瘤抑制率及动物死亡情况。结果 CAI分别和两种剂量的SAHA联合用药后,对Lewis肺癌细胞活力的抑制作用高于CAI组,细胞活力的抑制率分别达到46.09%±5.50%和54.43%±3.69%,差异均有统计学意义(P﹤0.01)。动物实验显示,与对照组相比,CAI组、SAHA组以及联合治疗组均抑制小鼠皮下肿瘤生长,且联合治疗组的肿瘤体积小于其他3组;除对照组外,各药物治疗组动物死亡率均低于20%。结论 SAHA与CAI联合使用能显著抑制Lewis肺癌细胞活力,并在Lewis肺癌细胞荷瘤动物中显现抗瘤增效作用。

Objective To study the inhibitory effect of the combination of CAI and SAHA on Lewis lung carcinoma （LLC） and evaluate the pharmacodynamic difference between the combined and single-agent treatment. Method SRB was performed to investigate the viability of LLC cells treated with CAI or SAHA alone, or in combination;LLC trans-planted model was established in C57 mice and the models were randomized into 4 groups, namely vehicle control group, CAI group, SAHA group and CAI＋SAHA combination group. The indicated solvent or drugs were administered continu-ously for 25 days and the change of body weight, tumor volume, tumor inhibition rate and death of mice were observed. Result The combinations of CAI and two different doses of SAHA showed stronger inhibitory effect on LLC cells via-bility than single CAI treatment. The inhibition rate of the combined treatment was 46.09%±5.50%and 54.43%±3.69%, （P〈0.01）, respectively. In vivo experiment showed that all treatments, including single CAI, single SAHA and combined treatment significantly inhibited LLC tumor growth compared with vehicle control. Moreover the tumor volume in mice treated with the combination was significantly smaller than that in control group and single-drug treated groups. Death rate of animals in all study groups but the control group was below 20%. Conclusion The combination of CAI and SAHA inhibits LLC cells viability significantly and shows synergistic anti-tumor effect in vivo.