PMC

The effects of cetuximab or erlotinib, gemcitabine, and radiation on EGFR signaling in vivo. Mice were treated as described in . Tumors were harvested on day 2 (A-D) or 12 (E-H) of treatment for immunoblotting. Data are from a single experiment (A, E) or the mean of 2-5 tumors ± standard error (B-D, F-H). Statistically significant differences of control versus treated* or EGFR^(Y845) versus EGFR^(Y1173)‡ are indicated (P<0.05).

The effects of gemcitabine and erlotinib on EGFR in pancreatic cancer cells. BxPc-3, Panc-1, or MPanc-96 cells were treated for 2 hours with 100nM (G1), 300nM (G2) (BxPC-3), 1uM (G1) or 3uM (G2) (Panc-1 and MPanc-96) gemcitabine. Cells were treated for 24 hours with 3uM erlotinib beginning 24 hours after gemcitabine exposure. Cells were harvested for immunoblotting at 24 and 48 hours post-gemcitabine (t_{24, 48}) or immediately after erlotinib (t24, 48). The amounts of the indicated proteins are shown from a single experiment for each cell line that is representative of at least 3 independent experiments.

The effects of cetuximab or erlotinib on gemcitabine-mediated radiosensitization in vivo. Athymic nude mice bearing subcutaneous BxPC-3 xenografts were treated with the indicated combinations of gemcitabine (120mg/kg), cetuximab (50mg/kg), erlotinib (100mg/kg), or radiation (1 Gy × 10) as illustrated (A). Data are expressed as the time to tumor volume doubling in response to treatments that began on day 0 (B). The tic marks represent the mean time to tumor volume doubling and the vertical bars represent the 95% confidence intervals. Data are from 2 tumors/mouse with 6-7 mice per treatment group. Statistically significant differences are indicated in .

The effects of erlotinib on cytotoxicity and radiosensitization in response to gemcitabine. BxPC-3 cells were treated for 2 hours with 100nM gemcitabine and/or for 72 hours with 3uM erlotinib according to schedules 1 or 2 as illustrated (A). Cytotoxicity was calculated as the fraction of surviving colonies in treated cells relative to the number of colonies in the untreated control cells (surviving fraction = 1) (B). The radiation survival curves in response to gemcitabine and/or erlotinib (C) were used to calculate the mean inactivation dose (MID). Radiation enhancement (ER) was calculated as the ratio of the MID for drug treated cells to non-drug treated cells (ER = 1). Data are from the mean of 3 independent experiments ± standard error (B, D) or a single experiment (C). Statistically significant differences between gemcitabine versus erlotinib plus gemcitabine (B) or radiation versus radiation plus gemcitabine and/or erlotinib (D) are shown (*P<0.05).