Luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) and bombesin antagonist RC-3940-II inhibit the growth of androgen-independent PC-3 prostate cancer in nude mice.
BACKGROUND
Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and luteinizing hormone-releasing hormone (LH-RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen-independent prostate cancer.


METHODS
LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured.


RESULTS
When the treatment was started, tumor volume in all groups was 70-80 mm3. After 4 weeks, tumor volume in the control animals injected with saline was 871 +/- 233 mm3 and that of animals treated with Cetrorelix only 197 +/- 61 mm3. The BN/GRP antagonist RC-3940-II also significantly reduced PC-3 tumor volume in nude mice to 122 +/- 20 mm3. The combination of Cetrorelix and RC-3940-II produced no additional inhibition. High-affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC-3940-II.


CONCLUSIONS
These findings demonstrate that LH-RH antagonists and BN/GRP antagonists inhibit the growth of the androgen-independent prostate cancer cell line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down-regulation of EGF receptors.
Jungwirth
A
A
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Galvan
G
G
Pinski
J
J
Halmos
G
G
Szepeshazi
K
K
Cai
R Z
RZ
Groot
K
K
Schally
A V
AV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology; D005755:Gastrins / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011467:Prostate / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018004:Receptors, Bombesin / Q000032:analysis / Q000502:physiology; D013739:Testosterone / Q000097:blood; D013936:Thymidine / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004338:Drug Combinations; D005755:Gastrins; D006727:Hormone Antagonists; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C096400:bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D066246:ErbB Receptors; C062876:cetrorelix; D001839:Bombesin; D013936:Thymidine