Abstract
Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 μg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In conRC-160 (50 μg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight, mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 624-629 |
| Number of pages | 6 |
| Journal | International Journal of Cancer |
| Volume | 98 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2002 |
| Externally published | Yes |
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Keywords
- Androgen-independent prostate cancer
- Antagonist of vasoactive intestinal peptide
- Growth hormone-releasing hormone
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity. / Plonowski, Artur; Varga, Jozsef L.; Schally, Andrew V; Krupa, Magdalena; Groot, Kate; Halmos, Gabor.
In: International Journal of Cancer, Vol. 98, No. 4, 01.04.2002, p. 624-629.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity
AU - Plonowski, Artur
AU - Varga, Jozsef L.
AU - Schally, Andrew V
AU - Krupa, Magdalena
AU - Groot, Kate
AU - Halmos, Gabor
PY - 2002/4/1
Y1 - 2002/4/1
N2 - Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 μg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In conRC-160 (50 μg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight, mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.
AB - Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 μg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In conRC-160 (50 μg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight, mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.
KW - Androgen-independent prostate cancer
KW - Antagonist of vasoactive intestinal peptide
KW - Growth hormone-releasing hormone
UR - http://www.scopus.com/inward/record.url?scp=0036533618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036533618&partnerID=8YFLogxK
U2 - 10.1002/ijc.10221
DO - 10.1002/ijc.10221
M3 - Article
C2 - 11920625
AN - SCOPUS:0036533618
VL - 98
SP - 624
EP - 629
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -