Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act synergistically in modulating the IGF system in rat prostate

Autor: C. Y. Ng, T. W. M. Chan, Moulay A. Alaoui-Jamali, Hung Huynh, Lesley Alpert
Rok vydání: 2001
Předmět:
Male
medicine.medical_specialty
medicine.drug_class
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Protein Serine-Threonine Kinases
Biology
Antiandrogen
Statistics
Nonparametric
Receptor
IGF Type 1
chemistry.chemical_compound
Insulin-like growth factor
Prostate cancer
5-alpha Reductase Inhibitors
Endocrinology
Prostate
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Enzyme Inhibitors
Insulin-Like Growth Factor I
Phosphorylation
Fulvestrant
Protein kinase B
Estradiol
Finasteride
Estrogen Antagonists
Drug Synergism
Epithelial Cells
Organ Size
Blotting
Northern
Antiestrogen
medicine.disease
Rats
Insulin-Like Growth Factor Binding Protein 3
medicine.anatomical_structure
chemistry
Apoptosis
Proto-Oncogene Proteins c-akt
Cell Division
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of Endocrinology. 171:109-118
ISSN: 1479-6805
0022-0795
DOI: 10.1677/joe.0.1710109
Popis: Prostate cancer is the most diagnosed invasive malignancy in males. Androgens and oestrogens have been implicated in the pathogenesis of prostate cancer. We report herein that the pure anti-oestrogen ICI 182,780 (ICI) reduces Ki-67 labelling index and IGF-I receptor levels in rat prostate. Increase of IGF-I mRNA and IGF-binding protein 3 (IGFBP-3) accumulation occur without any effect on prostate weight. Finasteride significantly decreases prostate weight and inhibits IGF-I gene expression. IGFBP-3 mRNA, Akt and phospho-Akt are not affected by finasteride. Co-administration of ICI plus finasteride reduces prostate weight by approximately 50% and causes acinar dilation with decreased luminal epithelial cell thickness. The acinar epithelial cells became atrophic and inactive with minimal cytoplasm. We also demonstrate a synergistic effect of ICI and finasteride on induction of IGFBP-3 accumulation and inhibition of Akt phosphorylation. Because the IGF and IGFBP-3 system plays an important role in prostate epithelial cell proliferation, apoptosis and tumour progression, the inhibitory effects of finasteride and ICI on IGF system may contribute to their anti-proliferative activity. These observations support a potential use of ICI in conjunction with finasteride in the prevention and/or treatment of prostate cancer.
Databáze: OpenAIRE
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