Furuta Y, Hall E R, Sanduja S, Barkley T, Milas L
Department of Experimental Radiotherapy, University of Texas M. D. Anderson Hospital and Tumor Institute at Houston 77030.
Cancer Res. 1988 Jun 1;48(11):3002-7.
We investigated whether there is a relationship between the production of eicosanoids by murine solid tumors and their response to the prostaglandin H (PGH) synthase inhibitor indomethacin. Three sarcomas, designated FSA, NFSA, and SA-NH, and two carcinomas, designated MCA-K and HCA-I, syngeneic to C3Hf/Kam mice were used. In general, FSA and NFSA produced more PGH synthase products than lipoxygenase products, whereas HCA-I produced both types of metabolites in large quantities. All three tumors responded well to indomethacin treatment by slowing their growth. In contrast, MCA-K and SA-NH tumors produced insignificant quantities of PGH synthase products, but substantial amounts of lipoxygenase products. Their growth was not affected by treatment with indomethacin. Indomethacin did not influence tumor cell survival either in vitro or in vivo, but it reduced the proportion of S-phase cells in the tumors. The antitumor effect of indomethacin was not reduced by immunosuppression of the tumor host and was independent of tumor immunogenicity, implying that indomethacin acted through nonimmunological mechanisms. Thus, the effectiveness of indomethacin was directly related to the ability of tumors to produce PGs. Consequently, the eicosanoid profile of tumors could serve as a valuable way to select patients likely to respond to indomethacin and other PGH synthase inhibiting agents.
我们研究了小鼠实体瘤产生类花生酸与它们对前列腺素H（PGH）合酶抑制剂吲哚美辛的反应之间是否存在关联。使用了三种与C3Hf/Kam小鼠同基因的肉瘤，分别命名为FSA、NFSA和SA-NH，以及两种癌，分别命名为MCA-K和HCA-I。一般来说，FSA和NFSA产生的PGH合酶产物比脂氧合酶产物多，而HCA-I大量产生这两种类型的代谢物。所有三种肿瘤对吲哚美辛治疗反应良好，生长速度减缓。相比之下，MCA-K和SA-NH肿瘤产生的PGH合酶产物量极少，但脂氧合酶产物量很大。它们的生长不受吲哚美辛治疗的影响。吲哚美辛在体外或体内均不影响肿瘤细胞存活，但它降低了肿瘤中S期细胞的比例。吲哚美辛的抗肿瘤作用不会因肿瘤宿主的免疫抑制而降低，且与肿瘤免疫原性无关，这意味着吲哚美辛通过非免疫机制起作用。因此，吲哚美辛的有效性与肿瘤产生前列腺素的能力直接相关。因此，肿瘤的类花生酸谱可以作为一种有价值的方法，用于选择可能对吲哚美辛和其他PGH合酶抑制剂有反应的患者。
