Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.

Abstract

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.

• Authors: T W Redding, A V Schally
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 81 Issue 1 Pg. 248-52 (Jan 1984) ISSN: 0027-8424 [Print] United States
• PMID: 6141560 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Luteolytic Agents
• Protein Precursors
• Triptorelin Pamoate
• Gonadotropin-Releasing Hormone
• Somatostatin
• Somatostatin-28

Topics

• Animals
• Castration
• Cell Line
• Cricetinae
• Drug Evaluation, Preclinical
• Gonadotropin-Releasing Hormone (analogs & derivatives, therapeutic use)
• Luteolytic Agents (therapeutic use)
• Male
• Mesocricetus
• Pancreatic Neoplasms (drug therapy)
• Protein Precursors (therapeutic use)
• Rats
• Rats, Inbred Strains
• Somatostatin (analogs & derivatives, therapeutic use)
• Somatostatin-28
• Structure-Activity Relationship
• Triptorelin Pamoate