The combination 5-fluorouracil/levamisole induces enhanced rat Kupffer cell-mediated cytotoxicity in vitro against the syngeneic colon adenocarcinoma cell line CC531.
The mode of action of the combination treatment 5-fluorouracil (5-FU) and levamisole in colorectal cancer patients is unknown. It is postulated that the beneficial effect may be explained by an immunomodulatory effect on Kupffer cell (KC) cytotoxicity. We evaluated the effect of levamisole (200 micrograms/ml) and 5-FU (10 microM) on rat KC cytotoxicity against syngeneic CC531 tumor cells. Viability of KCs was unaffected by 5-FU and/or levamisole. The combination did not enhance growth inhibition of CC531 compared to 5-FU alone. A significant increase in KC cytotoxicity was observed after 24-hr incubation with 5-FU/levamisole especially at an effector/target ratio of 10 (P < 0.05). 5-FU alone had no effect on KC cytotoxicity, while levamisole induced only a slight increase. Our in vitro data suggest that the additive effect of the combination 5-FU/levamisole on KC cytotoxicity may attribute to the beneficial effect of the adjuvant treatment in colorectal cancer patients.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000706:statistics & numerical data; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D007978:Levamisole / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D007978:Levamisole; D005472:Fluorouracil