Fig. 4
The antitumor activities of cetuximab and PEPDG278D in vivo correlate with EGFR downregulation. a Mice bearing subcutaneous tumors were treated with EP daily (SW48 tumors: days 2–20; HCT116 tumors: days 3–20; HT29 tumors: days 8–24; n = 12), cetuximab twice weekly (SW48 tumors: days 8–20; HT116 tumors: days 7–20; HT29 tumors: 10–24; n = 12–14), or EP daily plus PEPDG278D thrice weekly (SW48 tumors: days 8–20; HCT116 tumors: days 7–20; HT29 tumors: days 10–24; n = 12–14). EP, cetuximab, and PEPDG278D were administered ip at 0.5, 15, and 4 mg/kg per dose, respectively. Group average tumor sizes were 107–111 mm3 (SW48 tumors), 100–129 mm3 (HCT116 tumors), and 219–229 mm3 (HT29 tumors) at the beginning of treatment. Each value is mean ± SEM. ****P < 0.0001 by one-way ANOVA, followed by Tukey test for comparison with the control. b Western blotting of tumor homogenates (2 tumors per group). Tumors were harvested 24 h after the final treatment. See Fig. 1 legend for protein phosphorylation sites. c Plasma levels of mouse PEPD and PEPDG278D at 24 h after final PEPDG278D treatment. Each value is mean ± SD (n = 3). n.d., not significant by two-tailed unpaired t test. d, e Levels of soluble AREG and HB-EGF in control tumors. Each value is mean ± SD (n = 3). ***P < 0.001, ****P < 0.0001, by two-tailed unpaired t test