消炎痛与去甲二氢愈创木酸对巨噬细胞功能及肿瘤生长的相反作用。
Opposing effects of indomethacin and nordihydroguaiaretic acid on macrophage function and tumor growth.
作者信息
Suzuki M, Li J, Asakura T, Arai K
机构信息
Department of Surgery, Graduate Hospital, Philadelphia, Pennsylvania.
出版信息
Jpn J Cancer Res. 1994 Mar;85(3):306-14. doi: 10.1111/j.1349-7006.1994.tb02098.x.
The effects of indomethacin (INDO) and nordihydroguaiaretic acid (NDGA) were compared on macrophage function and tumor growth. Intraperitoneal injections (5 mg/kg/day, 6, 8 or 9 days) of INDO in C57BL/6 mice stimulated the cytotoxicity of peritoneal macrophages and inhibited growth of subcutaneous B16 melanoma, whereas NDGA injections suppressed macrophage cytotoxicity, increased macrophage prostaglandin-E2 (PGE2) release, and enhanced the tumor growth. Further, pretreatment of macrophages in vitro with the INDO group serum increased cytostasis against B16 tumor cells, while the use of NDGA group serum reduced it. Incubation of tumor-bearer's macrophages in vitro with INDO (10(-6) M and 10(-7) M) or 10(-6) M NDGA for 4 h reduced PGE2 release, but 10(-7) M NDGA markedly enhanced the PGE2 release. Our data indicate that INDO and NDGA are able to modulate the macrophage function directly, and produce opposing effects on macrophage function and tumor growth. Inhibitory actions of INDO and NDGA on the cyclooxygenase or lipoxygenase pathway of arachidonic acid metabolism appear to contribute to their effects.
比较了吲哚美辛（INDO）和去甲二氢愈创木酸（NDGA）对巨噬细胞功能和肿瘤生长的影响。在C57BL/6小鼠中腹腔注射INDO（5毫克/千克/天，共6、8或9天）可刺激腹腔巨噬细胞的细胞毒性，并抑制皮下B16黑色素瘤的生长，而注射NDGA则会抑制巨噬细胞的细胞毒性，增加巨噬细胞前列腺素E2（PGE2）的释放，并促进肿瘤生长。此外，用INDO组血清对体外巨噬细胞进行预处理可增强对B16肿瘤细胞的细胞生长抑制作用，而使用NDGA组血清则会降低该作用。将荷瘤小鼠的巨噬细胞与INDO（10⁻⁶M和10⁻⁷M）或10⁻⁶M NDGA在体外孵育4小时可减少PGE2的释放，但10⁻⁷M NDGA会显著增强PGE2的释放。我们的数据表明，INDO和NDGA能够直接调节巨噬细胞功能，并对巨噬细胞功能和肿瘤生长产生相反的影响。INDO和NDGA对花生四烯酸代谢的环氧合酶或脂氧合酶途径的抑制作用似乎与其作用有关。
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