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Inhibitory effects of analogs of luteinizing hormone‐releasing hormone on the growth of the androgen‐independent dunning R‐3327‐AT‐1 rat prostate cancer
Author(s) -
Pinski Jacek,
Reile Herta,
Halmos Gabor,
Groot Kate,
Schally Andrew V.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590112
Subject(s) - endocrinology , medicine , agonist , antagonist , androgen , luteinizing hormone , epidermal growth factor , hormone , chemistry , antiandrogen , receptor , biology
The effects of treatment with the luteinizing hormone‐releasing hormone (LH‐RH) antagonist SB‐75 and agonist [D‐Trp 6 ] LH‐RH were investigated in Copenhagen rats bearing the anaplastic, androgen‐independent Dunning R‐3327‐AT‐1 pros‐tatic adenocarcinoma implanted orthotopically into the ventral lobes of prostate glands. The LH‐RH antagonist SB‐75 and the LH‐RH agonist [D‐Trp 6 ] LH‐RH were administered from osmotic minipumps and the survival time of animals bearing this cancer was evaluated. Treatment with SB‐75 and [D‐Trp 6 ] LH‐RH significantly prolonged the mean survival time of rats by 4.1 days and 4.5 days, respectively. In cell cultures, proliferation of the AT‐1 cell line was strongly inhibited by the antagonist SB‐75, but only a moderate suppression of tumor cell growth in vitro was observed with the agonist [D‐Trp 6 ] LH‐RH. Receptor assays on Dunning R‐3327‐AT‐1 tumor membranes showed high‐affinity binding sites for LH‐RH, epidermal growth factor (EGF) and insulin‐like growth factor‐1 (IGF‐1). Receptors for EGF were significantly down‐regulated by treatment with SB‐75. Therapy with SB‐75 also decreased EGF levels in tumor tissue to non‐detectable levels, as measured by specific RIA. Our results demonstrate that the LH‐RH antagonist SB‐75 and agonist [D‐Trp 6 ] LH‐RH inhibit the growth of androgen‐independent Dunning R‐3327‐AT‐1 prostatic cancer in vivo and in vitro .