Figure 2.

Cancer‐associated fibroblasts (CAF) induce the acquired chemo‐resistance through a insulin‐like growth factor 2 (IGF2)/insulin‐like growth factor receptor‐1 (IGF‐1R) paracrine pathway. A, MTT assay of A549 cells treated with 400 nmol/L cisplatin (Cis), 150μmol/L etoposide (Eto) and 800 nmol/L vinorelbine ditartrate (VD), respectively, with or without CAF medium (CM) pretreated (n = 3). B, MTT assay of LCP1 cells treated with Cis, Eto and VD, respectively, with or without CAF medium (CM) pretreated (n = 3). C, mRNA expression of IGF2, SDF‐1, HGF, VEGFα, FGF, EGF, PDGF, CTGF, tenascin, TSP‐1 and fibronectin in CAF cells co‐culturing with or without LCP1 cells (n = 3). D, MTT assay of LCP1 cells treated with Cis, Eto and VD, respectively, with or without IGF2 pretreated (n = 3). E, MTT assay of LCP1 cells treated with Cis, Eto and VD, respectively, with or without CAF pre‐co‐cultured in the presence or absence of anti‐IGF2 (n = 3). F, mRNA expression of IGF‐1R, VEGFR, PDGFR, HGFR, CXCR4, EGFR, SDF‐1R and CTGFR in LCP1 cells with or without CAF co‐cultured (n = 3). G, MTT assay of LCP1 cells treated by Cis, Eto and VD, respectively, with or without IGF2 pretreated in the presence or absence of OSI‐906 (n = 3). H, A549 cells were isolated from A549‐bearing nude mice with CAF, IGF2, CAF and anti‐IGF2 treatment for 1 wk; the cell viability was analyzed in the addition of Cis, Eto or VD by MTT assay (n = 3). The data are presented as the means ± SEM from 3 independent experiments. * P < .05; ** P < .01; *** P < .001; ns, not statistically significant