Loewe等效线法计算盐霉素和索拉非尼合用抑制人肺腺癌细胞A549生长的协同 相加和拮抗浓度范围

Concentration Range of Synergism Addition and Antagonism of Combination of Salinomycin and Sorafenib for Inhibition of Human Lung Cancer Cell A549 Calculated with Loewe Isobologram Method

目的用改进的Loewe等效线模型法计算盐霉素和索拉非尼合用抑制人肺腺癌细胞A549生长的协同、相加和拮抗浓度范围。方法 MTT法检测药物对肿瘤细胞生长的抑制率,用Excel和ORIGIN 8.0进行数据处理,拟合得出单用药组和合用药组量效曲线及函数方程,计算在ED_(30)、ED_(50)、ED_(70)、ED_(90)时的合用指数。用合用组的量效曲线方程计算不同药物浓度水平合用时对应的抑制率,并分别代入各单药组量效曲线方程式,计算出相应的单用药物浓度值以及合用组各浓度水平的合用指数值,重构合用组药物浓度与合用指数值关系曲线图,并计算确定两药合用时协同、相加和拮抗效应的浓度范围。结果及结论在盐霉素+索拉非尼3种浓度比例合用的3种方式下,在ED_(30)、ED_(50)、ED_(70)、ED_(90)时,3种合用方式均体现为相加效应特征。按照本方法可以计算得出不同合用方式的相加、拮抗和协同的药物浓度范围,有利于帮助选择适当的合用比例。

Objective The concentration range of synergistic,additive and antagonistic effects of combination of salinomycin（ Sal） and sorafenib（ Sor） for inhibition of human lung cancer cell line A549 was calculated with Loewe isobologram extension method modified by our laboratory. Methods MTT assay was applied to assess the anti-proliferative effect. Excel and ORIGIN 8. 0 software were used to analyze the data,the concentrationresponse curves and functional equation were drawn,and the drug concentration of the single drug group and combined drug groups was measured when the inhibitory effect reached ED30,ED50,ED70,ED90. The efficacy of different concentrations was calculated according to the dose-effect curve equation of each combination group. The combination index（ CI） value was calculated for each dose level,and the dose-CI curve was re-drawn by using the Sal concentration of combination groups as the horizontal coordinate and the CI value as the vertical coordinate,setting the concentration-CI curve and equation,and assessing the concentration range of the synergistic,additive and antagonistic effect. Results and Conclusion The CIs of ED30,ED50,ED70,ED90 in the three patterns of Sal ＋ Sor combination were all shown as the additive effect（ 0. 9≤CI≤1. 1）. Using this method,the concentration ranges of Sal ＋ Sor combination could be obtained for the synergistic,additive and antagonistic effect in different combination patterns,which can be used to further analyze the two-drug combination under different conditions.