Fig. 1.

Icotinib enhanced the cytotoxicity of pemetrexed in vitro in a sequence-dependent manner. a Six NSCLC cell lines were exposed to pemetrexed and icotinib together or alone using constant ratios of the IC50 dose, respectively. b-g Cell lines were exposed to different combined models of pemetrexed and icotinib. #p < 0.05, I-P versus P-I. *p < 0.05, P + I versus P-I. Combination indexes (CI) between icotinib and pemetrexed were evaluated in six NSCLC cell lines. The CI value: < 0.9 represents synergistic effect, 0.9~1.1 represents addictive cytotoxicity, > 1.1 represents antagonistic effect. h The changes in cell morphology and spreading in PC-9 and A549 cells treated with pemetrexed and icotinib with the concentrations of two times of each cell’s IC50 at three sequences were observed. i Representative images and quantification of colony formation assay. Data are presented as mean ± SD of triplicate experiments, *p < 0.05