Combined antitumour activity of mitomycin C, 5-fluorouracil and interleukin-2 against human colon cancer cells.
Combined treatment of interleukin-2 (IL-2), 5-fluorouracil (5-FU) and mitomycin C (MMC) is reported to be effective against hepatic metastasis of colon carcinoma. To clarify this modality, we investigated lymphokine activated killer (LAK) activity of human peripheral lymphocytes on colon cancer cell lines by 51Cr release assay. LAK activity against Colo 205 cells by untreated lymphocytes was 12%, which increased to 25% upon the addition of 5-FU, but remained unchanged upon the addition of MMC. The combined antitumour activity of MMC or 5-FU with or without LAK-supernatant was evaluated by MTT assay; antitumour activity of MMC was increased by the addition of LAK-supernatant. The concentration of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) was increased in LAK-supernatant, and the antitumour activity of combined IFN-gamma and MMC was synergistic. The mechanism of this therapy seemed to be associated with both increased LAK activity by 5-FU and increased antitumour activity of MMC with IFN-gamma.
Ishihara
M
M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Watanabe
M
M
Kawano
Y
Y
Narai
S
S
Yasui
N
N
Otani
Y
Y
Teramoto
T
T
Kitajima
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007372:Interferons / Q000032:analysis; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D016685:Mitomycin / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016685:Mitomycin; D007372:Interferons; D005472:Fluorouracil