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In vitro activity of human chorionic gonadotropin (hCG)--doxorubicin conjugates against ovarian cancer cells

  • BACKGROUND Despite radical surgery and the introduction of novel chemotherapeutic agents, the prognosis of ovarian cancer remains poor. Since in the past the potential role of gonadotropins in the induction and progression of ovarian cancer has been discussed, we conjugated doxorubicin to human chorionic gonadotropin (hCG) in order to specifically target ovarian cancer cells. MATERIALS AND METHODS Doxorubicin was conjugated to hCG via glutaraldehyde. 48 hours post seeding, NIH:OVCAR 3 cellsBACKGROUND Despite radical surgery and the introduction of novel chemotherapeutic agents, the prognosis of ovarian cancer remains poor. Since in the past the potential role of gonadotropins in the induction and progression of ovarian cancer has been discussed, we conjugated doxorubicin to human chorionic gonadotropin (hCG) in order to specifically target ovarian cancer cells. MATERIALS AND METHODS Doxorubicin was conjugated to hCG via glutaraldehyde. 48 hours post seeding, NIH:OVCAR 3 cells were treated with various concentrations of hCG-conjugated and non-conjugated doxorubicin for 2 hours. Cells were cultured for a total of 168 hours. Cell growth was monitored by a crystal violet assay. RESULTS Conjugating doxorubicin to hCG resulted in an average specific uptake of 22 mol doxorubicin per mol protein (range 3.0-43.3 mol). Incubating NIH:OVCAR 3 cells for 2 hours with the conjugate led to a more than 8 fold increase of the IC50 values compared to non-conjugated doxorubicin (0.55 microM versus 4.43 microM). The antiproliferative activity of both conjugated and free doxorubicin was detectable up to 168 hours post treatment. CONCLUSIONS The present experiments clearly demonstrate a more than 8-fold increase in cytotoxicity of the conjugates compared to free doxorubicin. It was also shown that this effect was not restricted to an acute toxic event but that it resulted in a prolonged antiproliferative activity.show moreshow less

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Metadaten
Author:Eberhard BeckGND, D. Vincenti, P. Licht, A. Berkholz, W. Jäger, N. Lang, E. Merkle
Parent Title (English):In: Anticancer research 20(2000)5A, pg 3001-6
Document Type:Article
Language:English
Year of Publishing:2000
Date of Publication (online):2013/01/31
Release Date:2013/01/31
Tag:Antineoplastic Agents; Cell Division; Cell Survival; Chorionic Gonadotropin; Drug Synergism
First Page:3001
Last Page:3006
University Bibliography:Hochschulbibliografie
Licence (German):Creative Commons - Namensnennung, Nicht kommerziell, Keine Bearbeitung
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