Figure 4. Combinations of TRAP-Fc and therapeutic agents effectively inhibit growth of human pancreatic cancer cells in vitro and extend survival of tumor-bearing mice.

(A) BxPC3 pancreatic tumor cells (2×10⁴) were incubated with TRAP-Fc (30 μg/ml), either alone or in combination with cetuximab (20 μg/ml), trastuzumab (20 μg/ml), lapatinib (0.05 nM), erlotinib (0.2 nM), CI-1033 (0.5 nM), AG1478 (0.2 nM), gefitinib (0.004 nM), or gemcitabine (at 0.5 ng/ml). Cellular proliferation was measured in hexaplicates after 5 days, using the MTT assay. The experiment was repeated twice. (B) Female nude mice (6-week old) were inoculated subcutaneously with BxPC3 pancreatic cancer cells (2×10⁶). Once tumors became palpable, mice were randomized into four groups. The control group (9 mice; blue) is shown. The TRAP-Fc-treated group (6 mice; black line) was injected intraperitoneally with TRAP-Fc (100 μg). A third group (9 mice) was treated with gemcitabine (intraperitoneal injection, 25 mg/kg; green line), and a fourth group (6 mice; red) was treated with a combination of gemcitabine and TRAP-Fc. Mice were injected with TRAP-Fc on days: 19, 28, 32, 35, 39, 42, and 45. Gemcitabine injections were given on the same days and repeated three more times on days: 49, 52 and 55. Body weights were measured once a week, but no consistent differences were observed (data not shown).