Tibolone and 5alpha-dihydrotestosterone alone or in combination with an antiandrogen in a rat breast tumour model
| Autor: | G.B.T van Aalst, G.H. Deckers, M.E. De Gooyer, Helenius J. Kloosterboer, E.A.M Cremers, Herman A. M. Verheul |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
medicine.medical_specialty Antineoplastic Agents Hormonal medicine.drug_class Norpregnenes 9 10-Dimethyl-1 2-benzanthracene DMBA Administration Oral Tibolone Biology Placebo Antiandrogen Flutamide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Androgen Rats Androgen receptor Endocrinology Oncology chemistry Dihydrotestosterone Female medicine.drug |
| Zdroj: | European journal of cancer (Oxford, England : 1990). 38(3) |
| ISSN: | 0959-8049 |
| Popis: | Tibolone was combined with the antiandrogen flutamide to determine whether the inhibition of tumour growth in the prophylactic 7,12-dimethylbenz(a)anthracene (DMBA) rat model could be attributed to androgenic properties of one of its metabolites. The mean tumour load after tibolone (0.25 or 1.0 mg/kg twice daily orally for 10 weeks) was 125 and 255 versus 718 mm2 for placebo. The mean number of tumours were 1.2 and 2.0 versus 5.8, respectively. Combined with flutamide (10 mg/kg twice daily orally) both doses of tibolone did not result in an increase compared to placebo, but in significantly lower tumour loads (160 and 64 versus 718 mm2, respectively) and smaller numbers of tumours (0.8 and 1.0 versus 5.8, respectively). The differences between tibolone monotherapy and the combination groups with flutamide were not statistically significant indicating that flutamide did not reverse tibolone's inhibition of tumour growth. The positive control, 5alpha-dihydrotestosterone (DHT), entirely suppressed tumour development and flutamide abolished the inhibitory effect of DHT. Thus, unlike DHT, tibolone does not exert its beneficial effect in DMBA-induced tumours via the androgen receptor, but acts via different mechanisms. |
| Databáze: | OpenAIRE |
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