Gudewicz P W
Department of Physiology, Albany Medical College, NY 12208.
Cancer Lett. 1988 Sep-Oct;42(1-2):67-72. doi: 10.1016/0304-3835(88)90240-6.
The in vitro effects of methotrexate, vincristine, dexamethasone and adriamycin to modulate the antibody dependent cellular cytotoxicity (ADCC) reaction and secretion of superoxide (O2-) and hydrogen peroxide (H2O2) by phorbol myristate acetate (PMA) stimulated rat peritoneal macrophages were studied. Macrophage-mediated ADCC, as measured by the lysis of 51Cr-labeled IgG-coated sheep red blood cells in an 18 h assay, was significantly enhanced in the presence of 100 ng/ml of PMA. Treatment of macrophage monolayers for 24 h with vincristine (10(-5)-10(-7) M), dexamethasone (10(-5)-10(-9) M) and adriamycin (10(-6) M) inhibited ADCC by PMA stimulated macrophages. Vincristine, dexamethasone and adriamycin also inhibited the secretion of O2- and H2O2 by PMA stimulated macrophages at similar concentrations that reduced the ADCC reaction. Methotrexate (10(-3)-10(-7) M) did not inhibit either ADCC or O2- and H2O2 secretion by PMA stimulated macrophages. These results suggest that select anticancer drugs can inhibit macrophage mediated cytotoxicity of antibody coated target cells by suppressing the release of reactive oxygen intermediates by activated macrophages.
研究了甲氨蝶呤、长春新碱、地塞米松和阿霉素在体外对佛波酯（PMA）刺激的大鼠腹腔巨噬细胞调节抗体依赖性细胞毒性（ADCC）反应以及超氧化物（O2-）和过氧化氢（H2O2）分泌的影响。在18小时的试验中，通过检测51Cr标记的IgG包被的绵羊红细胞的裂解来测定巨噬细胞介导的ADCC，结果显示，在存在100 ng/ml PMA的情况下，ADCC显著增强。用长春新碱（10(-5)-10(-7) M）、地塞米松（10(-5)-10(-9) M）和阿霉素（10(-6) M）处理巨噬细胞单层24小时，可抑制PMA刺激的巨噬细胞的ADCC。长春新碱、地塞米松和阿霉素在降低ADCC反应的相似浓度下，也抑制PMA刺激的巨噬细胞分泌O2-和H2O2。甲氨蝶呤（10(-3)-10(-7) M）对PMA刺激的巨噬细胞的ADCC或O2-和H2O2分泌均无抑制作用。这些结果表明，某些抗癌药物可通过抑制活化巨噬细胞释放活性氧中间体，来抑制巨噬细胞介导的抗体包被靶细胞的细胞毒性。
