Inhibition of the growth of Caki-I human renal adenocarcinoma in vivo by luteinizing hormone-releasing hormone antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II.
BACKGROUND
Metastatic or recurrent renal cell carcinoma (RCC) is a therapeutic challenge because it is resistant to chemotherapy and external radiotherapy. No uniformly effective therapeutic agents are available for the management of patients with RCC. Hormones and growth factors may play a role in promoting the transformation and/or proliferation of kidney neoplasms.


METHODS
Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75), somatostatin analog RC-160, and bombesin antagonist RC-3940-II were tested for their effects on the growth of the Caki-I renal adenocarcinoma cell line xenografted into nude mice.


RESULTS
After 4 weeks of treatment, tumor volume was significantly (P < 0.01) decreased in animals receiving RC-160, to 167.5 +/- 34.2 mm3, compared with the control group (485.7 +/- 77.2 mm3). LH-RH antagonist SB-75 and bombesin antagonist RC-3940-II also significantly reduced the volume of Caki-I tumors, to 159.9 +/- 18.1 and 234.7 +/- 81.8 mm3, respectively. Somatostatin analog RC-160 decreased serum levels for growth hormone (GH) and insulin-like growth factor-I compared with controls. Treatment with RC-160, Cetrorelix, and RC-3940-II significantly reduced the number of high-affinity receptors for epidermal growth factor on Caki-I tumors.


CONCLUSIONS
LH-RH antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II effectively inhibit the growth of human Caki-I renal adenocarcinomas in nude mice. These peptide analogs should be considered for the therapy of patients with metastatic or recurrent RCC.
Jungwirth
A
A
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146, USA.
Schally
A V
AV
Halmos
G
G
Groot
K
K
Szepeshazi
K
K
Pinski
J
J
Armatis
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006727:Hormone Antagonists; D010446:Peptide Fragments; C096400:bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; C062876:cetrorelix; D001839:Bombesin