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

Sci Rep. 2019 Feb 27;9(1):2879. doi: 10.1038/s41598-019-39805-y.

Abstract

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 μg/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 mm3 for all treatment groups, the final mean tumor volumes reached were 282.0 ± 30.7 mm3 for the rhG-CSF-treated mice, 202.6 ± 18.1 mm3 for the gemcitabine-treated mice and 519.4 ± 62.9 mm3 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.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis
  • Cell Proliferation
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Therapy, Combination
  • Female
  • Gemcitabine
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Leukocytosis / chemically induced
  • Leukocytosis / immunology*
  • Leukocytosis / pathology
  • Mice
  • Mice, Nude
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Granulocyte Colony-Stimulating Factor
  • Gemcitabine