Figure 2.
A, effect of IGFBP-3 in resistance to BMS-536924. Rh41 cells were grown in 96-well plates at 3.5 × 103 per well in complete medium (10% FBS) for 24 h and then washed with PBS. The cells were either incubated with complete medium or 0.5% FBS-containing medium with 50 ng/mL human recombinant IGF-I for 4 h prior treatment with 0.1 μmol/L BMS-536924 and/or 1 μg/mL IGFBP-3 for 72 h. Cell growth was assessed using CellTiter96 aqueous nonradioactive cell proliferation assay kit (Promega). Columns, mean of absorbance measurements at 490 nm from representative experiment; bars, SE. *, P < 0.05 in Student’s t test. B, EGFR and ligands are overexpressed in BMS-536924 primary resistant cell lines. C, cathepsin family members are overexpressed in BMS-536924 primary resistant cell lines. B and C, expression data were detected by Affymetrix Genechip and RMA normalized; the mean expression values (y axis) of the 16 sensitive and the12 resistant cell lines with standard deviations are shown. D, IGFBP family members, IGFBP-2, IGFBP-3, IGFBP-5, and IGFBP-7, are more highly expressed in the BMS-536924 acquired resistant cell RD-1R compared with sensitive parental RD-1S cells. The fold changes (y axis) between BMS-536924 acquired resistant RD-1R and the sensitive parental RD-1S cells are shown.