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

被引:5
作者
IMAI, T
KATAGIRI, A
SAITO, K
TOMITA, Y
机构
[1] Department of Urology, Niigata University School of Medicine, Niigata, 951
关键词
NATURAL KILLER CELL; RENAL CELL CANCER; 5-FLUOROURACIL; INTERFERON-ALPHA; SUSCEPTIBILITY;
D O I
10.1016/0304-3835(95)03849-R
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 Cr-51-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 mu g/ml. An adhesion assay showed that preincubation of ACHN with 5FU and IFN-alpha did not alter the adhesion of IFN-alpha-activated Mt 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.
引用
收藏
页码:191 / 197
页数:7
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