Interferon-alpha-induced protection of renal cell cancer cell line from lysis by natural killer cells and increase of susceptibility by treatment with 5-fluorouracil.
We have shown previously that interferon (IFN)-alpha reduces the sensitivity of renal cell cancer (RCC) cell lines ACHN and KRC/Y to lysis by lymphokine-activated killer (LAK) cells. The close relationship between natural killer (NK) cells and LAK cells prompted us to investigate whether IFN-alpha pretreatment also affects the sensitivity of ACHN cells to lysis by NK cells or IFN-alpha-activated NK cells. A 51Cr-release cytotoxicity assay demonstrated that pretreatment of ACHN with IFN-alpha decreased their susceptibility to NK cells and IFN-alpha-activated NK cells in a dose-dependent manner. Moreover, to investigate the usefulness of 5-fluorouracil (5FU) for combination with IFN-alpha therapy, we examined the effect of preincubation with 5FU on the susceptibility of ACHN. IFN-alpha-induced protection of ACHN from lysis by IFN-alpha-activated NK cells weakened in the presence of 5FU at 0.2 microgram/ml. An adhesion assay showed that preincubation of ACHN with 5FU and IFN-alpha did not alter the adhesion of IFN-alpha-activated NK cells. A cold target competition analysis did not show any difference between untreated and 5FU and/or IFN-alpha-treated competitors. These results suggest that one of the mechanisms of 5FU for combination with IFN-alpha therapy might depend on changes of RCC cells in intrinsic lysability involving a post-binding stage of the lytic cycle to NK cells.
Imai
T
T
Department of Urology, Niigata University School of Medicine, Japan.
Katagiri
A
A
Saito
K
K
Tomita
Y
Y
D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D005472:Fluorouracil