PI3K/Akt抑制剂联合西妥昔单抗对人肺癌细胞的体外抑制作用

目的探讨PI3K/Akt抑制剂LY294002单独或联合西妥昔单抗对人肺癌细胞株A549的作用,以期为肺癌临床治疗方案的选择、用药顺序提供新的理论依据。方法选用西妥昔单抗和LY294002,分析单药及不同浓度和联合作用方式对A549细胞增殖的影响;计算IC50值和CI值,分析药物联合作用的效应是协同、相加抑或拮抗。结果单独作用时,西妥昔单抗与LY294002最大抑制率分别为(57.3±6.2)%、(56.2±6.0)%;联合作用时,LY294002→西妥昔单抗序贯给药(CI=0.41)比同步应用(CI=0.73)可增强疗效,其最大抑制率分别为(84.9±7.5)%和(79.0±7.3)%。结论两药对A549细胞增殖均具有抑制作用,LY294002→西妥昔单抗序贯联合应用对A549细胞的增殖抑制率最高。

Effects of cetuximab combined inhibitor of PI3K/Akt on proliferation of human lung carcinoma cell lines A549

Objective To evaluate the effects of cetuximab and inhibitor of phosphatidylinositol 3-kinase/Akt（PI3K/Akt） LY294002 on proliferation of non-small cell lung cancer （NSCLC） lines A549 alone and in different sequences of combinations. Methods Cetuximaband LY294002, alone or in combination were administrated to A549 cells with different sequences. The ICso and the combination index （CI） of these two agents were calculated. Results The single agent of cetux- imab and LY294002 inhibited the proliferation of A549 cells in a dose-dependent manner. The proliferation inhibition rates of A549 cells were （57.3±6.2）% and （56.2±6.0）%. When cetuximab was combined with LY294002 synchronously, the maximal inhibitory effect of the proliferation inhibition rate of A549 was （79.0±7.3）%. At that time,the CI of the two agents at IC50 points was 0.73, suggested that they had obvious synergistic activity. While,when LY294002 was followed by cetuximab,the maximal inhibitory effect of the proliferation inhibition rate of A549 was （84.9±7.5）% and the CI of the two agents at ICso points was 0.41. Conclusion The single agent of cetuximab and LY294002 can inhibit the proliferation of A549 cells,and they have obvious synergistic activity. The optimal treatment sequence is LY294002 followed by cetux- imab, and it can obtain obvious synergistic activity and conduce to less doses in clinical application.