TY - JOUR
T1 - Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix inhibits growth of DU-145 human androgen-independent prostate carcinoma in nude mice and suppresses the levels and mRNA expression of IGF-II in tumors
AU - Lamharzi, Najib
AU - Schally, Andrew V.
AU - Koppán, Miklós
N1 - Funding Information:
We are grateful to Professor Jurgen Engel, ASTA Medica (Frankfurt/Main, Germany) for Cetrorelix. We thank Patricia Armatis and Dr. Kate Groot for their technical assistance. The gifts of materials used in RIA from the National Hormone and Pituitary Program (NHPP) of the National Institute of Diabetes and Digestives and Kidney Diseases (NIDDK) are appreciated. The sequencing of the IGF-II cDNA was performed by Brandon Blakey (Genome Systems, Inc., St. Louis, MO). The work described in this paper was supported by the Medical Research Service of the Veterans Affairs Department, CaP Cure Foundation Research Award, and a grant from ASTA Medica (Frankfurt on Main, Germany) (all to A.V.S.).
PY - 1998/10/16
Y1 - 1998/10/16
N2 - In previous studies, we showed that LH-RH antagonist Cetrorelix inhibits the growth of DU-145 and PC-3 human androgen-independent prostate cancers in nude mice. To investigate the mechanisms involved, we treated male nude mice bearing xenografts of DU-145 human androgen-independent prostate cancer with Cetrorelix at a dose of 100 μg/animal subcutaneously (s.c.) once a day. Tumor growth, serum and tumor levels of IGF-I and -II as well as the mRNA expression of IGF-I and -II in tumors were evaluated. After 8 weeks of treatment, final volume and weight of DU-145 tumors in mice treated with Cetrorelix were significantly decreased compared with controls and serum IGF-1 showed a significant reduction. Therapy with Cetrorelix also reduced by 84% the levels of IGF-II in DU-145 tumor tissue compared with controls, but did not affect the concentration of IGF-I. RT-PCR analyses revealed a high expression of mRNA for IGF-II, but not for IGF-I in DU-145 tumors. Treatment with Cetrorelix decreased the expression of IGF-II mRNA by 78% (p<0.01) as compared with controls. Our study indicates that LH-RH antagonist Cetrorelix may inhibit the growth of DU-145 human androgen-independent prostate cancers by decreasing the production and mRNA expression of IGF-II by the tumor tissue. This also suggests that LH-RH antagonist Cetrorelix could interfere with the signal transduction pathways involving IGF-II, leading to tumor growth inhibition. Copyright (C) 1998 Elsevier Science B.V.
AB - In previous studies, we showed that LH-RH antagonist Cetrorelix inhibits the growth of DU-145 and PC-3 human androgen-independent prostate cancers in nude mice. To investigate the mechanisms involved, we treated male nude mice bearing xenografts of DU-145 human androgen-independent prostate cancer with Cetrorelix at a dose of 100 μg/animal subcutaneously (s.c.) once a day. Tumor growth, serum and tumor levels of IGF-I and -II as well as the mRNA expression of IGF-I and -II in tumors were evaluated. After 8 weeks of treatment, final volume and weight of DU-145 tumors in mice treated with Cetrorelix were significantly decreased compared with controls and serum IGF-1 showed a significant reduction. Therapy with Cetrorelix also reduced by 84% the levels of IGF-II in DU-145 tumor tissue compared with controls, but did not affect the concentration of IGF-I. RT-PCR analyses revealed a high expression of mRNA for IGF-II, but not for IGF-I in DU-145 tumors. Treatment with Cetrorelix decreased the expression of IGF-II mRNA by 78% (p<0.01) as compared with controls. Our study indicates that LH-RH antagonist Cetrorelix may inhibit the growth of DU-145 human androgen-independent prostate cancers by decreasing the production and mRNA expression of IGF-II by the tumor tissue. This also suggests that LH-RH antagonist Cetrorelix could interfere with the signal transduction pathways involving IGF-II, leading to tumor growth inhibition. Copyright (C) 1998 Elsevier Science B.V.
KW - DU-145 human androgen-independent prostate cancers
KW - Insulin-like growth factor II (IGF-II)
KW - Luteinizing hormone-releasing hormone antagonist (LH-RH)
KW - mRNA suppression
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U2 - 10.1016/S0167-0115(98)00119-0
DO - 10.1016/S0167-0115(98)00119-0
M3 - Article
C2 - 9809814
AN - SCOPUS:0032538353
VL - 77
SP - 185
EP - 192
JO - Regulatory Peptides
JF - Regulatory Peptides
SN - 0167-0115
IS - 1-3
ER -
