Enhancement of chemotherapeutic effects by recombinant human granulocyte colony-stimulating factor on implanted mouse bladder cancer cells (MBT-2).
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered intraperitoneally in combination with multidrug chemotherapy using methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C, or for the combination, MVAC) to C3H/He mice (5-week-old females) after experimental carcinoma, MBT-2, a transplantable transitional cell carcinoma of the urinary bladder had been implanted. The effects of therapy were studied. The animal groups consisted of: (1) control (no drug administration), (2) rhG-CSF (100 micrograms/kg/d, from days 8 through 42 after MBT-2 implantation, except for the days when MVAC was administered), (3) high-dose MVAC (2 mg/kg of M, 0.2 mg/kg of V, 2 mg/kg of A, and 4 mg/kg of C once a week for 3 weeks), (4) low-dose MVAC (one-quarter of the high dose), (5) high-dose MVAC with rhG-CSF, and (6) low-dose MVAC with rhG-CSF. In an in vitro system, rhG-CSF did not show any effect on the proliferation of MBT-2 cells or exert any influences on A's tumor proliferation-suppressing action on MBT-2. However, in an in vivo system, concomitant administration of rhG-CSF significantly enhanced the tumor-suppressing effect of the MVAC therapy, as did rhG-CSF alone. The greatest effect was observed in the group receiving high-dose MVAC plus rhG-CSF. These result suggested that rhG-CSF-stimulated granulocytes may exert antitumor activity on tumor cells severely damaged by chemotherapeutic agents at a relatively high concentration. The survival rate was improved to some degree even by administration of rhG-CSF alone. Although further study is required to elucidate the action mechanism of rhG-CSF, these results suggest that rhG-CSF may be useful clinically to enhance the activity of antitumor agents and not only through its ability to alleviate granulocytopenia or prevent its development.
Akaza
H
H
Department of Urology, University of Tsukuba, Japan.
Fukushima
H
H
Koiso
K
K
Aso
Y
Y
D000380:Agranulocytosis / Q000517:prevention & control; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor