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Adriamycin‐induced resistance to natural killer (NK)‐mediated cytotoxicity
Author(s) -
Wood William J.,
Lotzová Eva
Publication year - 1989
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19890715)64:2<396::aid-cncr2820640210>3.0.co;2-z
Subject(s) - cytotoxicity , lysis , medicine , pharmacology , natural killer cell , cell culture , cytolysis , immunology , effector , doxorubicin , microbiology and biotechnology , cancer research , chemotherapy , biology , in vitro , biochemistry , genetics
Studies were done to determine the susceptibility of a colon carcinoma cell line, LoVo, to natural killer (NK) mediated lysis after exposure of the tumor cells to Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). LoVo cells were exposed to ADR (0.4 μg/ml) for various time intervals and then tested for sensitivity to lysis by NK cells from the peripheral blood of normal donors in a sodium chromate (Cr 51 ) release cytotoxicity assay. Exposure of tumor targets to ADR induced a resistance to NK‐mediated lysis. Susceptibility to lysis decreased progressively to approximately 60% of control levels after 72 hours of ADR exposure. The induction of resistance was dependent on ADR dose, but did not magnify with doses greater than 0.4 μg/ml. When target cells were allowed to recover from ADR in fresh medium for 48 hours, complete reversal of the ADR effect was seen. The effect of interleukin‐2 (IL‐2) stimulation on the NK lysis of LoVo also was tested. IL‐2‐stimulated effector cells demonstrated enhanced cytotoxicity to LoVo targets and were able to overcome the ADR‐induced resistance to lysis. The mechanism of resistance does not appear to be related to the altered binding of effectors to chemotherapy‐treated targets, as suggested by single cell assay results.