Tumoricidal effect of human macrophage-colony-stimulating factor against human-ovarian-carcinoma-bearing athymic mice and its therapeutic effect when combined with cisplatin.
The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM-CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect.
Adachi
T
T
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Mano
H
H
Shinohara
Y
Y
Nakanishi
T
T
Suzuki
T
T
Ino
K
K
Kato
N
N
Okamoto
T
T
Nawa
A
A
Goto
S
S
D000380:Agranulocytosis / Q000188:drug therapy; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D016173:Macrophage Colony-Stimulating Factor; D002945:Cisplatin