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Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors in ovarian cancer and its correlation to human chorionic gonadotropin–doxorubicin sensitivity

  • Objective Ovarian cancer cell lines and tissues express gonadotropin receptors. Conjugation of cytostatics to ligands of these receptors may increase the specificity of cytotoxic drugs. Study design Toxicity of doxorubicin–human chorionic gonadotropin conjugates was determined in 4 ovarian cancer cell lines. Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors were analyzed before and after treatment with human chorionic gonadotropin, epidermal growthObjective Ovarian cancer cell lines and tissues express gonadotropin receptors. Conjugation of cytostatics to ligands of these receptors may increase the specificity of cytotoxic drugs. Study design Toxicity of doxorubicin–human chorionic gonadotropin conjugates was determined in 4 ovarian cancer cell lines. Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors were analyzed before and after treatment with human chorionic gonadotropin, epidermal growth factor, and 8-bromo-cyclic adenosine monophosphate with a nested reverse transcriptase–polymerase chain reaction approach. Results Toxicity of human chorionic gonadotropin–doxorubicin conjugates was increased compared with unconjugated doxorubicin in OVCAR-3 cells. However, drug conjugates failed to demonstrate increased toxicity in other cell lines, especially after preincubation with human chorionic gonadotropin. All cell lines expressed luteinizing hormone/human chorionic gonadotropin receptors. Receptor expression in OVCAR-3 cells was not effected by human chorionic gonadotropin, endothelial growth factor, or 8-bromo-cyclic adenosine monophosphate treatment. In other cell lines, receptor expression was down-regulated by these agents. Conclusion Cytotoxic activity of doxorubicin was increased specifically by conjugation to human chorionic gonadotropin. However, the regulation of luteinizing hormone/human chorionic gonadotropin receptor expression and other compounds may reduce the drug-uptake of the conjugates.show moreshow less

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Metadaten
Author:Gerhard Gebauer, Natalia Mueller, Tanja Fehm, Alexander Berkholz, Eberhard BeckGND, Wolfram Jaeger, Peter Licht
Parent Title (German):In: American Journal of Obstetrics & Gynecology 190 (2004), Iss. 6, pp. 1621-1628
Document Type:Article
Language:English
Year of Publishing:2004
Date of Publication (online):2013/01/30
Release Date:2013/01/30
First Page:1621
Last Page:1624
University Bibliography:Hochschulbibliografie
Licence (German):Creative Commons - Namensnennung, Nicht kommerziell, Keine Bearbeitung
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