Programmed cell death (apoptosis) in pancreatic cancers of hamsters after treatment with analogs of both luteinizing hormone-releasing hormone and somatostatin.
Programmed cell death (apoptosis) in pancreatic cancers of hamsters after treatment with analogs of both luteinizing hormone-releasing hormone and somatostatin.
复制标题
用黄体生成素释放激素和生长抑素类似物治疗后仓鼠胰腺癌的程序性细胞死亡（细胞凋亡）。
DOI：
10.1073/pnas.86.5.1643
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发表时间：
1989
影响因子：
11.1
通讯作者：
Schally,AV
中科院分区：
文献类型：
--
作者：
Szende,B;Zalatnai,A;Schally,AV
雌性叙利亚金仓鼠与N-亚硝基双用促黄体生成素释放激素的6-D-色氨酸类似物的长效微囊制剂治疗（2-氧代丙基）胺（BOP）诱导的胰腺导管癌。生长抑素类似物D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH 2（RC-160），释放15微克/天;以及这两种肽的组合。在BOP初始给药后24周开始类似物治疗。与BOP对照相比，这些处理导致所有动物的显著更好的存活;存活的肽处理的动物的体重显著高于BOP对照的体重。所有15只BOP对照动物都患有胰腺癌。在用RC-160治疗的组中，四只仓鼠没有肿瘤，而用[D-Trp 6]LH-RH治疗导致七只无肿瘤动物，并且RC-160和[D-Trp 6]LH-RH的组合导致来自15只的组的八只无肿瘤动物。在这些动物中仅发现胚细胞瘤前病变。在开始肽处理后60天处死的所有肽处理组中的动物的平均肿瘤重量显著低于BOP对照组。在各种肽处理组之间没有观察到显著差异。在组织学上，类似物处理的仓鼠肿瘤显示出程序性细胞死亡（凋亡）特征的显著消退性变化。这种细胞凋亡可能是由于长期使用这些下丘脑激素类似物对肿瘤细胞的激素作用所致。我们目前的数据证实了[D-Trp 6]LH-RH和RC-160的长效微胶囊对胰腺癌的有益作用，并提出了这些肽的作用模式。从这些研究中可以预见到应用下丘脑激素类似物治疗人类胰腺癌的可行性。
Female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine (BOP)-induced ductal pancreatic cancers were treated with long-acting microcapsular preparations of the 6-D-tryptophan analog of luteinizing hormone-releasing hormone [( D-Trp6]LH-RH), releasing 25 micrograms/day; the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), liberating 15 micrograms/day; and the combination of these two peptides. Therapy with analogs was initiated 24 weeks after initial administration of BOP. These treatments resulted in significantly better survival of all animals as compared to BOP controls; body weights of surviving peptide-treated animals were significantly higher than those of the BOP controls. All 15 BOP-control animals had pancreatic cancers. In the group treated with RC-160 four hamsters were free of tumors, whereas therapy with [D-Trp6]LH-RH resulted in seven tumor-free animals, and combination of RC-160 and [D-Trp6]LH-RH resulted in eight tumor-free animals from groups of 15. Only preblastomatous lesions were found in these animals. Average tumor weight of animals in all peptide-treated groups, sacrificed 60 days after beginning the peptide treatment, was significantly lower than that of BOP controls. No significant differences were seen between the various peptide-treated groups. Histologically, analog-treated tumors of hamsters showed striking regressive changes characteristic of programmed cell death (apoptosis). This apoptosis presumably resulted from hormonal effects on tumor cells from prolonged treatment with these analogs of hypothalamic hormones. Our present data confirm the beneficial effect of long-acting microcapsules of [D-Trp6]LH-RH and RC-160 on pancreatic carcinoma and suggest a mode of action for these peptides. The feasibility of applying this treatment with analogs of hypothalamic hormones to human pancreatic carcinoma can be envisioned from these studies.