Tokiwa University, Faculty of Human Science, Department of Health and Nutrition, 1-430-1 Miwa, Mito, Ibaraki, 310-8585, Japan.
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan.
Eur J Pharmacol. 2022 Nov 5;934:175206. doi: 10.1016/j.ejphar.2022.175206. Epub 2022 Aug 31.
Although lipopolysaccharide (LPS) is reported effective for cancer, developmental application as anti-tumour therapeutic agents have been prevented due to its severe toxicity. Since antitumour action of LPS was suggested to be partly related to the function of neutrophil, we investigated the effects of granulocyte colony stimulating factor (G-CSF), a cytokine enhancing neutrophil function, on antitumour activity of bacterial LPS against a murine syngeneic hepatoma MH134.
Effect of G-CSF (30 μg/kg i.v. pretreatment, 4 days) and LPS (20μg/mouse) on tumor growth and survival days of mice bearing MH134 hepatoma were monitored.
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 tumour growth. Although G-CSF pretreatment alone did not inhibit the growth, once combined with LPS, significant inhibition was observed compared with LPS group. Tumour regression was demonstrated in combination group (6/12 mice), and survival of the mice in the combination group exceeded those of the LPS monotherapy group without enhancing the body weight loss.
Combination of G-CSF and LPS prominently inhibit the tumour growth and elongated the survival days without enhancing a toxic response to LPS treatment.
虽然脂多糖（LPS）已被报道对癌症有效，但由于其严重的毒性，其在癌症发展中的应用作为抗肿瘤治疗剂受到了阻碍。由于 LPS 的抗肿瘤作用部分与中性粒细胞的功能有关，我们研究了细胞因子粒细胞集落刺激因子（G-CSF）对细菌 LPS 对鼠同源性肝癌 MH134 的抗肿瘤活性的影响。
观察 G-CSF（30μg/kg 静脉预处理，4 天）和 LPS（20μg/只）对携带 MH134 肝癌的小鼠肿瘤生长和存活天数的影响。
4 天的 G-CSF 30μg/kg 治疗可使中性粒细胞水平显著增加。在 MH134 肝癌荷瘤小鼠中，LPS 显著抑制肿瘤生长。虽然单独的 G-CSF 预处理不能抑制生长，但与 LPS 联合使用时，与 LPS 组相比，观察到明显的抑制作用。联合组显示出肿瘤消退（6/12 只小鼠），并且联合组小鼠的存活时间超过了 LPS 单一疗法组，而没有增强对 LPS 治疗的毒性反应。
G-CSF 和 LPS 的联合使用显著抑制肿瘤生长并延长存活时间，而不会增强对 LPS 治疗的毒性反应。
