Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.
Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.
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含有细胞毒性自由基的黄体生成素释放激素类似物对体内不依赖雌激素的 MXT 小鼠乳腺癌生长的影响。
DOI：
10.1097/00001813-199204000-00006
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发表时间：
1992
影响因子：
2.3
通讯作者：
Janaky,T
中科院分区：
文献类型：
--
作者：
Szepeshazi,K;Schally,AV;Juhasz,A;Nagy,A;Janaky,T
在携带MXT（（3.2）/Ovex）雌激素非依赖性乳腺肿瘤的雌性BDF小鼠中检测了细胞毒性促黄体生成激素释放激素（LH-RH）类似物AJ-004（与甲氨蝶呤（MTX）连接的激动剂[D-Lys 6] LH-RH）、T-98（与戊二酰-2-（羟甲基）蒽醌偶联的[D-Lys 6] LH-RH）（G-HMAQ）和T-121/B（含两个G-HMAQ残基的拮抗剂）。所有三种细胞毒性LH-RH类似物，从Alzet渗透微型泵给药3周，对肿瘤生长产生显著抑制。T-98和T-121/B的作用上级优于单独用等摩尔剂量的细胞毒性部分蒽醌或LH-RH载体处理所获得的作用。我们假设细胞毒性LH-RH类似物具有激素和细胞毒性的组合活性，在体内给药后毒性降低。这是第一次证明体内肿瘤抑制靶向LH-RH类似物轴承细胞毒性自由基。
Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys 6] LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys 6] LH-RH coupled to glutaryl-2-(hydroxymethyl) anthraquinone)(G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF, mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administration In vivo. This is the first demonstration of In vivo tumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals.