Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.
Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.
复制标题
通过下丘脑激素类似物抑制动物模型中胰腺癌的生长。
DOI：
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发表时间：
1985
影响因子：
11.1
通讯作者：
A. Schally
中科院分区：
文献类型：
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作者：
T. Redding;A. Schally
利用胰腺腺泡癌和导管癌的动物模型，我们研究了下丘脑激素类似物对肿瘤生长的影响。在患有胰腺腺泡肿瘤DNCP-322的Wistar/刘易斯大鼠中，长期给予[L-5-Br-Trp 8]生长抑素-14显著降低肿瘤重量和体积。生长抑素-28和生长抑素环的环六肽类似物（Pro-Phe-D-Trp-Lys-Thr-Phe）不能影响该肿瘤的生长。促黄体生成素释放激素[D-Trp 6]LH-RH的激动剂类似物也显著降低了该模型中的肿瘤重量和体积，并降低了睾酮水平和腹侧前列腺和测试的重量。在叙利亚仓鼠轴承导管型胰腺癌，慢性给药[L-5-Br-Trp 8]生长抑素减少肿瘤重量和体积。与对照动物相比，肿瘤体积的百分比变化显著降低。在一个实验中，生长抑素的环六肽也抑制该肿瘤的生长。[D-Trp 6]LH-RH，每日两次给药或以微囊形式注射用于恒定控制释放，显著降低肿瘤重量和体积，并抑制血清睾酮水平。移植胰腺肿瘤后4天去势的仓鼠显示这些肿瘤的重量和体积显著减少。这表明胰腺癌可能至少部分是性激素敏感的。[D-Trp 6]LH-RH可能通过抑制雄激素而抑制胰腺癌的生长。生长抑素类似物可能通过抑制胃肠激素对肿瘤细胞的释放或刺激作用（或两者）来减少胰腺导管癌和腺泡癌的生长。通过长期施用生长抑素类似物和[D-Trp 6]LH-RH对胰腺肿瘤动物模型的抑制表明，这些化合物应被考虑用于开发胰腺癌的新激素疗法。
Using animal models of acinar and ductal pancreatic cancer, we investigated the effect of analogs of hypothalamic hormones on tumor growth. In Wistar/Lewis rats bearing the acinar pancreatic tumor DNCP-322, chronic administration of [L-5-Br-Trp8]somatostatin-14 significantly decreased tumor weights and volume. Somatostatin-28 and the cyclic hexapeptide analog of somatostatin cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) failed to influence the growth of this tumor. The agonistic analog of luteinizing hormone-releasing hormone [D-Trp6]LH-RH also significantly decreased tumor weight and volume in this model and reduced testosterone levels and the weights of the ventral prostate and tests. In Syrian hamsters bearing ductal type of pancreatic carcinoma, chronic administration of [L-5-Br-Trp8]somatostatin diminished tumor weights and volume. The percentage change in tumor volume was significantly decreased when compared to control animals. In one experiment, cyclic hexapeptide of somatostatin also inhibited growth of this tumor. [D-Trp6]LH-RH, given twice daily or injected in the form of microcapsules for constant controlled release, significantly decreased tumor weight and volume and suppressed serum testosterone levels. Hamsters castrated 4 days after transplantation of the pancreatic tumors showed a significant decrease in weight and volume of these tumors. This suggests that pancreatic cancers may, at least in part, be sex hormone sensitive. [D-Trp6]LH-RH may decrease the growth of pancreatic carcinomas by suppressing androgens. Somatostatin analogs reduce the growth of pancreatic ductal and acinar cancers, probably by inhibiting the release or stimulatory action of gastrointestinal hormones on tumor cells (or both). Inhibition of animal models of pancreatic tumors by chronic administration of somatostatin analogs and [D-Trp6]LH-RH suggests that these compounds should be considered for the development of a new hormonal therapy for cancer of the pancreas.