Liarozole, an antitumor drug, modulates cytokeratin expression in the Dunning AT-6sq prostatic carcinoma through in situ accumulation of all-trans-retinoic acid
| Autor: | Frans C. S. Ramaekers, R. Van Ginckel, G. Daneels, M. Borgers, M.-C. Coene, J.A. Schalken, M. Moeremans, G. Smets, J. Van Wauwe, R. De Coster |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Pathology medicine.medical_specialty Urology Immunoblotting Retinoic acid Antineoplastic Agents Tretinoin chemistry.chemical_compound Cytokeratin Random Allocation Prostate medicine Carcinoma Tumor Cells Cultured Animals Vimentin Liarozole Epithelioma Dose-Response Relationship Drug business.industry Imidazoles Antibodies Monoclonal Prostatic Neoplasms Organ Size medicine.disease Immunohistochemistry Rats Inbred F344 Squamous carcinoma Rats Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology chemistry Cancer research Carcinoma Squamous Cell Keratins business Neoplasm Transplantation |
| Zdroj: | The Prostate. 27(3) |
| ISSN: | 0270-4137 |
| Popis: | Liarozole showed antitumoral activity in the Dunning AT-6sq, an androgen-independent rat prostate carcinoma. To investigate its potential mechanism of action, the effects of the drug doses (ranging from 3.75 to 80 mg/kg b.i.d.) on endogenous plasma and tissue all-trans-retinoic acid levels and on the differentiation status of the tumor cells were evaluated. To follow modulation of differentiation, cytokeratins were localized in the (un)treated tumors by immunocytochemistry and quantitatively determined by immunoblotting. Results showed that liarozole statistically significantly reduced tumor weight from 30 mg/kg upwards and induced accumulation of all-trans-retinoic acid both in plasma and tumors. In the tumors, a statistically significant accumulation was already noted from 7.5 mg liarozole/kg upwards. Concomitantly, the differentiation status shifted from a keratinizing towards a non-keratinizing squamous carcinoma, which was further confirmed by the cytokeratin profile of the carcinoma (presence of CK 8, 10, 13, 14, 18, 19). Immunoblotting revealed an overall decrease in cytokeratin content, except for CK 8. These findings suggest that the antitumoral properties of liarozole might be related to an increase in the degree of tumor differentiation through accumulation of all-trans-retinoic acid. |
| Databáze: | OpenAIRE |
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