Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness

  • Authors:
    • Jose M. Arencibia
    • Andrew V. Schally
    • Magdalena Krupa
    • Ana M. Bajo
    • Attila Nagy
    • Karoly Szepeshazi
    • Artur Plonowski
  • View Affiliations

  • Published online on: September 1, 2001     https://doi.org/10.3892/ijo.19.3.571
  • Pages: 571-577
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Abstract

Receptors for luteinizing hormone-releasing hormone (LHRH), expressed by ovarian cancers, can be used for targeting chemotherapeutic compounds more selectively to these tumors. We investigated the effects of cytotoxic LHRH analog AN-152, consisting of doxorubicin (DOX)-14-O-hemiglutarate linked to the ε-amino group of [D-Lys6]LHRH, on the growth of LHRH receptor-positive ES-2 human ovarian cancer line xenografted into nude mice. A single injection of AN-152, at a dose of 345 nmol/20 g body weight, caused a 34.5% reduction (P<0.05) in tumor growth after 28 days, while its cytotoxic moiety DOX was inactive at the same dose. Since the overexpression of certain growth factors and/or their receptors, such as vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and HER-2/neu, as well as various oncogenes like c-fos and c-jun, is associated with unfavorable prognosis and contributes to progressive growth of ovarian carcinomas, their mRNA levels were analyzed by RT-PCR. Treatment with AN-152 significantly (P<0.05) reduced the expression of EGFR, VEGF, c-fos and c-jun, to 49%, 48%, 55% and 58% respectively, compared to controls. HER-2/neu mRNA expression was also decreased to non-detectable levels. Conversely, DOX decreased non-significantly the expression levels for EGFR by 32%, VEGF 35%, both c-fos and c-jun approximately 20% and HER-2/neu by only 15%. In conclusion, cytotoxic LHRH analog AN-152 could be considered for chemotherapy of ovarian cancers expressing LHRH receptors.

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September 2001
Volume 19 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Arencibia JM, Schally AV, Krupa M, Bajo AM, Nagy A, Szepeshazi K and Plonowski A: Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness. Int J Oncol 19: 571-577, 2001
APA
Arencibia, J.M., Schally, A.V., Krupa, M., Bajo, A.M., Nagy, A., Szepeshazi, K., & Plonowski, A. (2001). Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness. International Journal of Oncology, 19, 571-577. https://doi.org/10.3892/ijo.19.3.571
MLA
Arencibia, J. M., Schally, A. V., Krupa, M., Bajo, A. M., Nagy, A., Szepeshazi, K., Plonowski, A."Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness". International Journal of Oncology 19.3 (2001): 571-577.
Chicago
Arencibia, J. M., Schally, A. V., Krupa, M., Bajo, A. M., Nagy, A., Szepeshazi, K., Plonowski, A."Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness". International Journal of Oncology 19, no. 3 (2001): 571-577. https://doi.org/10.3892/ijo.19.3.571