Antitumoral effect of maintained neutrophilia induced by rhG-CSF in a murine model of pancreatic cancer

Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 mu g/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6-7 mice per group). Compared to the controls, both the rhG-CSF-and gemcitabine-treated mice showed significantly suppressed tumor growth by day 4 (p < 0.001 and p = 0.013 respectively). From a mean starting volume of 106.9 +/- 3.1 mm(3) for all treatment groups, the final mean tumor volumes reached were 282.0 +/- 30.7 mm(3) for the rhG-CSF-treated mice, 202.6 +/- 18.1 mm(3) for the gemcitabine-treated mice and 519.4 +/- 62.9 mm(3) for the control mice (p < 0.004 and p < 0.01, respectively, vs. control). The rhG-CSF-treated tumors showed higher percentage necrosis than those treated with gemcitabine (37.4 +/- 4.6 vs. 7.5 +/- 3.0; p < 0.001). This is the first report of a clear anti-tumoral effect of rhG-CSF when used in monotherapy against pancreatic cancer. Since rhG-CSF administration is known to be associated with very few adverse events, it may offer an attractive alternative in the clinical treatment of pancreatic cancer.