Abstract
We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, and the luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-3095 at a dose of 20 μg/day and Cetrorelix (100 μg/day), significantly reduced the volume of ES-2 tumors by 63.0% (P < 0.01) and 38.0% (P < 0.05) respectively, after 44 days of treatment, as compared with controls. The combination of RC-3095 with Cetrorelix inhibited the growth of ES-2 tumors by 66.2% (P < 0.01). Serum levels of LH were significantly decreased in the groups treated with Cetrorelix alone and/or in combination with RC-3095. RT-PCR analyses revealed that the expression of mRNA for receptors of GRP (GRPR/BRS-1) and Neuromedin B (NMBR/BRS-2) on tumors was significantly decreased in all the treated groups. The expression of mRNA for epidermal growth factor receptors (EGFR) on tumors was reduced by 36.5% (P < 0.05) in the animals treated with Cetrorelix and by 72.5% (P < 0.05) in the group that received the combination of RC-3095 with Cetrorelix. Our results indicate that the bombesin antagonist RC-3095 and the LH-RH antagonist Cetrorelix inhibit effectively the growth of ES-2 ovarian cancers in nude mice. These antagonists and their combination could be considered for the therapy of patients with ovarian cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 37-45 |
| Number of pages | 9 |
| Journal | Cancer Letters |
| Volume | 171 |
| Issue number | 1 |
| DOIs | |
| State | Published - Aug 28 2001 |
| Externally published | Yes |
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Keywords
- Bombesin/gastrin-releasing peptide
- Cancer therapy
- Luteinizing hormone-releasing hormone
- Ovarian tumors
ASJC Scopus subject areas
- Cancer Research
- Molecular Biology
- Oncology
Cite this
Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix. / Chatzistamou, Ioulia; Schally, Andrew V; Szepeshazi, Karoly; Groot, Kate; Hebert, Francine; Arencibia, Jose M.
In: Cancer Letters, Vol. 171, No. 1, 28.08.2001, p. 37-45.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix
AU - Chatzistamou, Ioulia
AU - Schally, Andrew V
AU - Szepeshazi, Karoly
AU - Groot, Kate
AU - Hebert, Francine
AU - Arencibia, Jose M.
PY - 2001/8/28
Y1 - 2001/8/28
N2 - We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, and the luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-3095 at a dose of 20 μg/day and Cetrorelix (100 μg/day), significantly reduced the volume of ES-2 tumors by 63.0% (P < 0.01) and 38.0% (P < 0.05) respectively, after 44 days of treatment, as compared with controls. The combination of RC-3095 with Cetrorelix inhibited the growth of ES-2 tumors by 66.2% (P < 0.01). Serum levels of LH were significantly decreased in the groups treated with Cetrorelix alone and/or in combination with RC-3095. RT-PCR analyses revealed that the expression of mRNA for receptors of GRP (GRPR/BRS-1) and Neuromedin B (NMBR/BRS-2) on tumors was significantly decreased in all the treated groups. The expression of mRNA for epidermal growth factor receptors (EGFR) on tumors was reduced by 36.5% (P < 0.05) in the animals treated with Cetrorelix and by 72.5% (P < 0.05) in the group that received the combination of RC-3095 with Cetrorelix. Our results indicate that the bombesin antagonist RC-3095 and the LH-RH antagonist Cetrorelix inhibit effectively the growth of ES-2 ovarian cancers in nude mice. These antagonists and their combination could be considered for the therapy of patients with ovarian cancer.
AB - We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, and the luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-3095 at a dose of 20 μg/day and Cetrorelix (100 μg/day), significantly reduced the volume of ES-2 tumors by 63.0% (P < 0.01) and 38.0% (P < 0.05) respectively, after 44 days of treatment, as compared with controls. The combination of RC-3095 with Cetrorelix inhibited the growth of ES-2 tumors by 66.2% (P < 0.01). Serum levels of LH were significantly decreased in the groups treated with Cetrorelix alone and/or in combination with RC-3095. RT-PCR analyses revealed that the expression of mRNA for receptors of GRP (GRPR/BRS-1) and Neuromedin B (NMBR/BRS-2) on tumors was significantly decreased in all the treated groups. The expression of mRNA for epidermal growth factor receptors (EGFR) on tumors was reduced by 36.5% (P < 0.05) in the animals treated with Cetrorelix and by 72.5% (P < 0.05) in the group that received the combination of RC-3095 with Cetrorelix. Our results indicate that the bombesin antagonist RC-3095 and the LH-RH antagonist Cetrorelix inhibit effectively the growth of ES-2 ovarian cancers in nude mice. These antagonists and their combination could be considered for the therapy of patients with ovarian cancer.
KW - Bombesin/gastrin-releasing peptide
KW - Cancer therapy
KW - Luteinizing hormone-releasing hormone
KW - Ovarian tumors
UR - http://www.scopus.com/inward/record.url?scp=0035964475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035964475&partnerID=8YFLogxK
U2 - 10.1016/S0304-3835(01)00543-2
DO - 10.1016/S0304-3835(01)00543-2
M3 - Article
C2 - 11485826
AN - SCOPUS:0035964475
VL - 171
SP - 37
EP - 45
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -