Wood W J, Lotzová E
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Cancer. 1989 Jul 15;64(2):396-403. doi: 10.1002/1097-0142(19890715)64:2<396::aid-cncr2820640210>3.0.co;2-z.
Studies were done to determine the susceptibility of a colon carcinoma cell line, LoVo, to natural killer (NK) mediated lysis after exposure to the tumor cells to Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). LoVo cells were exposed to ADR (0.4 micrograms/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 (Cr51) 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 micrograms/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.
开展了多项研究，以确定结肠癌细胞系LoVo在暴露于阿霉素（ADR，多柔比星；阿德里亚实验室，俄亥俄州哥伦布市）后对自然杀伤（NK）介导的裂解作用的敏感性。将LoVo细胞暴露于阿霉素（0.4微克/毫升）不同时间间隔，然后在铬酸钠（Cr51）释放细胞毒性试验中检测其对来自正常供体外周血NK细胞裂解作用的敏感性。将肿瘤靶细胞暴露于阿霉素会诱导其对NK介导的裂解产生抗性。暴露于阿霉素72小时后，裂解敏感性逐渐降低至对照水平的约60%。抗性的诱导取决于阿霉素剂量，但剂量大于0.4微克/毫升时不会增强。当靶细胞在新鲜培养基中从阿霉素作用下恢复48小时后，可见阿霉素效应完全逆转。还测试了白细胞介素-2（IL-2）刺激对LoVo细胞NK裂解作用的影响。IL-2刺激的效应细胞对LoVo靶细胞表现出增强的细胞毒性，并且能够克服阿霉素诱导的裂解抗性。如单细胞试验结果所示，抗性机制似乎与效应细胞与化疗处理靶细胞的结合改变无关。
