Inhibition of growth of MCF-7 MIII human breast carcinoma in nude mice by treatment with agonists or antagonists of LH-RH.
Inhibition of growth of MCF-7 MIII human breast carcinoma in nude mice by treatment with agonists or antagonists of LH-RH.
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LH-RH 激动剂或拮抗剂治疗对裸鼠 MCF-7 MIII 人乳腺癌生长的抑制作用。
DOI：
10.1007/bf01811962
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发表时间：
1992
影响因子：
3.8
通讯作者：
Schally,AV
中科院分区：
文献类型：
--
作者：
Yano,T;Korkut,E;Pinski,J;Szepeshazi,K;Milovanovic,S;Groot,K;Clarke,R;Comaru-Schally,AM;Schally,AV
人类乳腺癌（MCF-7 MIII）表现出雌激素不依赖但雌激素应答的表型，将其移植到8 - 9周龄的完整雌性胸腺裸鼠中，不补充雌激素。在这个模型中，我们研究了现代黄体生成素释放激素（LH-RH）拮抗剂SB-75和激动剂D-Trp6-LH-RH的抑制作用。这些类似物以持续递送系统（微胶囊和微颗粒）的形式给药。第一次试验，治疗时间为10周。治疗9周后，最初仅在SB-75组发现肿瘤体积有明显抑制，但最终肿瘤体积均被D-Trp6-LH-RH和SB-75显著抑制。第二组实验在肿瘤移植后70天开始治疗，持续治疗6周。通过测量肿瘤体积、肿瘤体积变化百分比和肿瘤重量，SB-75或D-Trp6-LH-RH慢性治疗似乎完全阻止了肿瘤的生长。血清雌二醇被抑制到检测不到的水平，黄体生成素水平也下降。组织学上，治疗肿瘤的退行性变化是由于肿瘤细胞凋亡（程序性细胞死亡）的增强。膜受体检测显示，用SB-75或D-Trp6-LH-RH处理后，肿瘤细胞中LH-RH结合位点下调。结果表明，从持续递送系统释放的拮抗剂SB-75可以与激动剂D-Trp6-LH-RH一样有效地抑制MCF-7 MIII肿瘤的生长，但速度更快。rh - rh拮抗剂SB-75具有直接阻断垂体-性腺轴和无副作用的特点，可能被认为是一种治疗乳腺癌的新型激素。
Human breast carcinoma (MCF-7 MIII), which exhibits an estrogen-independent but estrogenresponsive phenotype, was xenografted in 8–9-week-old intact female athymic nude mice without estrogen supplementation. In this model, we investigated inhibitory effects of the modern luteinizing hormonereleasing hormone (LH-RH) antagonist SB-75 and the agonist D-Trp6-LH-RH. The analogs were administered in the form of sustained delivery systems (microcapsules and microgranules). In the first experiment, treatment lasted 10 weeks. After 9 weeks of treatment, a significant inhibition of tumor volume was first found only in the group treated with SB-75, but the final tumor volume was significantly suppressed both by D-Trp6-LH-RH and SB-75. In the second experiment, treatment was started 70 days after tumor transplantation and was continued for 6 weeks. Chronic treatment with SB-75 or D-Trp6-LH-RH appeared to completely arrest tumor growth as measured by tumor volume, percentage change in tumor volume, and tumor weight. Serum estradiol was suppressed to undetectable levels and LH levels were also diminished. Histologically, the regressive changes in the treated tumors were due to the enhancement of apoptosis (programmed cell death) of tumor cells. Membrane receptor assays showed that LH-RH binding sites were down-regulated in tumor cells after treatment with SB-75 or D-Trp6-LH-RH.The results indicate that the antagonist SB-75, released from sustained delivery systems, can inhibit the growth of MCF-7 MIII tumors as effectively as the agonist D-Trp6-LH-RH, but more rapidly. In view of its immediate blockade of the pituitary-gonadal axis and the absence of side effects, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of breast cancer.