Supplementary Figures 1 - 18 from Metformin Sensitizes EGFR-TKI–Resistant Human Lung Cancer Cells In Vitro and In Vivo through Inhibition of IL-6 Signaling and EMT Reversal

PDF file - 1625K, Supplementary Figure 1 IC50 values of different cell lines to TKIs under indicated conditions Supplementary Figure 2 BrdU incorporation assay for H1975 cells. Supplementary Figure 3 Expression of OCT-1 and LKB1 in different cell lines used in the current study. Supplementary Figure 4 Metformin decreases invasion and motility of erlotinib-resistant H1650-M3 cells. Supplementary Figure 5 Metformin decreases SNAIL expression in TKI-resistant human lung cancer cells. Supplementary Figure 6 Quantification of blots shown in Fig. 2E. Supplementary Figure 7 Metformin decreases IL-6 gene transcription in TKI-resistant cell lines. Supplementary Figure 8 Metformin reverses TKI resistance in IL-6 overexpressing PC-9psb cells. Supplementary Figure 9 Inhibition of IL-6 signaling is essential for metformin to overcome erlotinib resistance in H1650-M3 cells. Supplementary Figure 10 Body weight of PC-9GR xenografts Supplementary Figure 11 Serum insulin levels and glucose levels from xenografts established by PC-9GR cells. Supplementary Figure 12 Metformin in combination with gefitinib suppresses tumor growth in PC-9 xenografts Supplementary Figure 13 Metformin in combination with gefitinib increased the expression of E-cadherin and decreased the expression of Vimentin in tumor sections of PC-9 xenografts. Supplementary Figure 14 Quantification of blots in Fig. 6D. Supplementary Figure 15 Western blotting analysis of the expression of indicated markers on protein extracts obtained from harvested tumors of the gefitinib group and gefitinib+metformin group. Supplementary Figure 16 Metformin in combination with gefitinib decreases expression of phosphorylation of AKT and STAT3 in xenografts established by PC-9GR cells. Supplemental Figure 17 Metformin overcomes TKI resistance through EMT reversal and IL-6 signaling inhibition. Supplemental Figure 18 Metformin disrupts the evil axis of TGFbeta/IL-6, EMT, CSCs and TKI resistance.