# LH-RH AGONISTS AND ANTAGONISTS IN PROSTATE CANCER

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 1990 · $140,105

## Abstract

Analogs of luteinizing hormone-releasing hormone (LH-RH) given
alone and in combination will be tested in rats bearing androgen-
dependent Dunning R3327H adenocarcinomas, Dunning R-3327AT
androgen-independent anaplastic prostate tumors, and other models
of prostate cancers and in nude mice or nude rats with transplanted
human prostate cancer cell lines e.g., LNCaP, DU-145, and PC-3.
Our studies will include:  (1) the investigation of prostate tumor
growth inhibition induced by:  (a) controlled delivery system based
on the microcapsules of the agonist D-Trp-6-LH-RH in poly (D,L-
lactide-co-glycolide) (pLGA) for once-a-month administration  and
a comparison of the effectiveness of microcapsules given alone and
with various combinations, in inhibiting tumor growth; (b)
combinations of D-Trp-6-LH-RH microcapsules with microcapsules of
somatostatin superanalog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH
(RC-160); (c) New LH-RH antagonists such as (Ac-D-Nal (2), D-Phe
(pC1)2, D-Tr3p, D-Cit6, D2-Ala10) LH-RH, (SB-30), or another
related antagonist, administered as microcapsule formulations in
pLGA; d) combinations of LH-RH antagonist microcapsules with
somatostatin analog RC-160.  Studies (1 alpha-d) will include long-
term experiments in Dunning R3327H model to establish the duration
of response.  (2) continued synthesis of various agonists and
antagonists of LH-RH containing cytotoxic radicals such as
Melphalan, Aziridine and Mitomycin C, the evaluation of their
binding to LH-RH receptors and testing of their effects in animal
models of prostate cancer as targeted hormonal carriers for
chemotherapeutic agents; (3) in vitro evaluation in rat and human
prostate cancer cell lines of direct inhibitory effects of LH-RH
agonists and antagonists, somatostatin analog RC-160 and antitumor
effect of peptides with cytotoxic radicals; (4) Biochemical studies
such as DNA synthesis and measurement of protein phosphorylation.
(5) Determination of tumor membrane receptors for LH-RH,
somatostatin and prolactin in animals treated with LH-RH and
somatostatin analogs.  Steroid (androgen) receptors will be also
measured.  (6) Determination of blood levels of IGF-1, tumor
content of EGF, IGF-1, and the levels of receptors for EGF and IGF-
1.  (7) Histological and histomorphometric evaluations to correlate
morphological changes with tumor regression.  The aim of this
project will be to:  a) improve the response to LH-RH agonists in
prostate cancer by combined therapy with somatostatin analog RC-
160; b) evaluate the usefulness of the new LH-RH antagonists and
targeted LH-RH analogs with cytotoxic radicals for the inhibition
of this tumor; c) elucidate the mechanism of action of these
analogs.

## Key facts

- **NIH application ID:** 3179430
- **Project number:** 5R01CA040003-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **SAM.gov UEI:** XNY5ULPU8EN6
- **Principal Investigator:** ANDREW V SCHALLY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $140,105
- **Award type:** 5
- **Project period:** 1985-09-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179430

## Citation

> US National Institutes of Health, RePORTER application 3179430, LH-RH AGONISTS AND ANTAGONISTS IN PROSTATE CANCER (5R01CA040003-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179430. Licensed CC0.

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