Kikuchi Y, Imaizumi E, Kataoka Y, Hirata J, Kita T, Tode T, Nagata I
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
Cancer Immunol Immunother. 1996 Dec;43(5):257-61. doi: 10.1007/s002620050331.
The aim of this study was to elucidate the effect of intraperitoneal (i.p.) instillations of granulocyte-colony-stimulating factor (G-CSF) and/or interleukin-2 (IL-2) on ascites formation and the survival time of nude mice with malignant ascites, produced by i.p. inoculation of human ovarian cancer cells. When the nude mice were treated with medium alone, ascites was observed in all mice 28 days after tumor inoculation. When the mice were treated with cis-diamminedichloroplatinum(II) (cisplatin) alone, G-CSF alone or IL-2 alone, it took 35 days for the ascites to form in all mice. When cisplatin was combined with G-CSF or IL-2, one of ten mice did not form ascites during the observation period. Surprisingly, when G-CSF and IL-2 were simultaneously administered, ascites formation was not observed in any mice. Although i.p. treatment with cisplatin alone significantly prolonged the survival time, compared to medium alone, the lytic activity of spleen cells against HRA cells was significantly suppressed. When G-CSF or IL-2 was combined with cisplatin, the suppression by cisplatin was eliminated and subsequently resulted in a prolongation of the survival time. When G-CSF was combined with IL-2, both the peritoneal and splenic macrophages/ monocytes were stimulated and the splenic lytic activity was about double that following treatment with G-CSF alone on IL-2 alone, suggesting that complete inhibition of ascites formation results not only from a significant increase of the peritoneal macrophages but also from enhancement of the lytic activity. Two mice, died from dissemination of tumor in the abdominal cavity, but eight mice survived without tumor for more than 90 days. As confirmed by monitoring body weight and hematocrit, G-CSF and IL-2 seemed to have no adverse effect. From these results, we conclude that a combination therapy with G-CSF and IL-2 might be of clinical use for inhibiting large amounts of ascites, which may inhibit therapeutic effects for ovarian cancer patients.
本研究的目的是阐明腹腔内注射粒细胞集落刺激因子（G-CSF）和/或白细胞介素-2（IL-2）对腹腔接种人卵巢癌细胞所致恶性腹水裸鼠腹水形成及生存时间的影响。当裸鼠仅用培养基处理时，在肿瘤接种后28天所有小鼠均出现腹水。当小鼠单独用顺二氯二氨铂（顺铂）、单独用G-CSF或单独用IL-2处理时，所有小鼠腹水形成需35天。当顺铂与G-CSF或IL-2联合使用时，十只小鼠中有一只在观察期内未形成腹水。令人惊讶的是，当同时给予G-CSF和IL-2时，任何小鼠均未观察到腹水形成。虽然单独腹腔注射顺铂与单独用培养基相比显著延长了生存时间，但脾细胞对人卵巢癌细胞（HRA）的杀伤活性被显著抑制。当G-CSF或IL-2与顺铂联合使用时，顺铂的抑制作用被消除，随后导致生存时间延长。当G-CSF与IL-2联合使用时，腹膜和脾脏巨噬细胞/单核细胞均受到刺激，脾脏杀伤活性约为单独用G-CSF或单独用IL-2处理后的两倍，这表明腹水形成的完全抑制不仅源于腹膜巨噬细胞的显著增加，还源于杀伤活性的增强。两只小鼠死于腹腔内肿瘤播散，但八只小鼠无瘤存活超过90天。通过监测体重和血细胞比容证实，G-CSF和IL-2似乎没有不良影响。从这些结果我们得出结论，G-CSF和IL-2联合治疗可能在临床上用于抑制大量腹水，而大量腹水可能会抑制卵巢癌患者的治疗效果。
