@article{GebauerMuellerFehmetal.2004, author = {Gebauer, Gerhard and Mueller, Natalia and Fehm, Tanja and Berkholz, Alexander and Beck, Eberhard and Jaeger, Wolfram and Licht, Peter}, title = {Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors in ovarian cancer and its correlation to human chorionic gonadotropin-doxorubicin sensitivity}, series = {In: American Journal of Obstetrics \& Gynecology 190 (2004), Iss. 6, pp. 1621-1628}, journal = {In: American Journal of Obstetrics \& Gynecology 190 (2004), Iss. 6, pp. 1621-1628}, pages = {1621 -- 1624}, year = {2004}, abstract = {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 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.}, language = {en} }