Background: Severe toxicity of lipopolysaccharide (LPS) have prevented its clinical use for cancer treatment so far. We have demonstrated that LPS potentiated the activity of PMN and suggested that LPS induced antitumor effect partially depend on PMN. Then, we investigated the effects of granulocyte colony stimulating factor (G-CSF), a cytokine enhancing neutrophil function, on antitumor activity of bacterial LPS against a murine syngeneic hepatoma MH134.
Methods: G-CSF (30 μg/kg) was administered for successive 4 days intravenously and LPS (20 μg/mouse) was administered with MH134 hepatoma intradermally on day 0, and tumor growth and survival days of mice bearing MH134 hepatoma were monitored.
Results: 4 day treatment of G-CSF 30 μg/kg increased the neutrophil level with statistical significance. On the MH134 hepatoma bearing mice, LPS significantly inhibited the tumor growth. Although G-CSF pretreatment alone did not inhibit the growth, once combined with LPS, significant inhibition was observed compared with LPS group. Tumor regression was demonstrated in combination group (6/12 mice), and the mice without tumor burden survived exceeding those of the LPS monotherapy group without enhancing the body weight loss.
Conclusions: G-CSF potentiated the antitumor effect of LPS and elongated the survival days of mice bearing MH134 hepatoma without enhancing the toxic response to LPS.