Kollmorgen G M, King M M, Kosanke S D, Do C
Cancer Res. 1983 Oct;43(10):4714-9.
Studies were designed to determine if treatment with indomethacin influenced the growth of a transplantable, metastatic, rat mammary tumor. Female, Wistar-Furth inbred rats were fed either a standard chow diet or a semipurified diet containing 2, 5, 10, or 20% stripped corn oil. Indomethacin was given in drinking water, and rats consumed between 2.5 and 3.0 mg indomethacin/kg body weight/day. Feeding of diets and initiation of treatment with indomethacin were started when rats were weaned (21 days old) and continued until they were killed. Approximately 5 X 10(3) mammary tumor cells (DMBA-4) were injected into the fat pad of the sixth mammary gland which is adjacent to the right inguinal lymph node. Each dietary/treatment group consisted of at least 10 rats. Since indomethacin inhibits prostaglandin synthesis, two other groups of non-tumor-bearing rats were used to determine if dietary fat and treatment with indomethacin either influenced prostaglandin E2 production (in vitro) by mononuclear cells from the spleen or altered serum levels of fatty acids. Results indicated that: (a) the rate of tumor growth in untreated rats was significantly greater when the dietary fat content was either 10 or 20% compared to diets containing either 2 or 5% fat; (b) the tumor growth-promoting effects of 10 and 20% fat diets were completely abrogated in rats treated with indomethacin; (c) treatment with indomethacin also inhibited tumor growth in rats fed diets containing either 2 or 5% fat; (d) synthesis of prostaglandin E2 by mononuclear cells from the spleens of untreated rats increased as the dietary fat content increased; (e) in indomethacin-treated rats, prostaglandin E2 synthesis was inhibited in all dietary groups and was not dependent on dietary fat; and (f) in both untreated and indomethacin-treated rats, the serum concentrations of oleic and linoleic acids were influenced to the same extent by dietary fat.
开展了多项研究以确定吲哚美辛治疗是否会影响一种可移植、具有转移性的大鼠乳腺肿瘤的生长。给雌性Wistar-Furth近交系大鼠喂食标准饲料或含有2%、5%、10%或20%精炼玉米油的半纯化饲料。吲哚美辛添加到饮用水中，大鼠每天摄入2.5至3.0毫克吲哚美辛/千克体重。大鼠断奶（21日龄）时开始喂食饲料并开始用吲哚美辛治疗，持续至处死。将约5×10³个乳腺肿瘤细胞（DMBA-4）注射到右侧腹股沟淋巴结附近的第六乳腺脂肪垫中。每个饮食/治疗组至少有10只大鼠。由于吲哚美辛会抑制前列腺素合成，另外两组未患肿瘤的大鼠用于确定饮食脂肪和吲哚美辛治疗是否会影响脾脏单核细胞的前列腺素E2生成（体外）或改变血清脂肪酸水平。结果表明：（a）与含2%或5%脂肪的饲料相比，饲料脂肪含量为10%或20%时，未治疗大鼠的肿瘤生长速度明显更快；（b）在接受吲哚美辛治疗的大鼠中，10%和20%脂肪饲料促进肿瘤生长的作用完全消除；（c）吲哚美辛治疗也抑制了喂食含2%或5%脂肪饲料大鼠的肿瘤生长；（d）未治疗大鼠脾脏单核细胞的前列腺素E2合成随着饲料脂肪含量的增加而增加；（e）在吲哚美辛治疗的大鼠中，所有饮食组的前列腺素E2合成均受到抑制，且不依赖于饮食脂肪；（f）在未治疗和吲哚美辛治疗的大鼠中，油酸和亚油酸的血清浓度受饮食脂肪的影响程度相同。
