Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers

  • Authors:
    • Carsten Gründker
    • Jennifer Ernst
    • Madita D. Reutter
    • B. Michael Ghadimi
    • Günter Emons
  • View Affiliations

  • Published online on: June 7, 2011     https://doi.org/10.3892/or.2011.1340
  • Pages: 629-635
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Abstract

Pancreatic cancer is the fourth commonest cause of cancer-related mortality across the world. Because of the poor response to conventional chemotherapy, small molecules, radiation therapy and surgery, development of new targeted therapies is necessary. In the present study, we have analyzed expression of the luteinizing hormone releasing hormone (LHRH) receptor in specimens of human pancreatic cancers. Furthermore, we have investigated in vitro and in vivo whether the cytotoxic LHRH agonist AEZS-108 (AN-152) induces apoptosis in human pancreatic cancer cells that express LHRH receptors. LHRH receptor expression in tumor specimens of human pancreatic cancers was assessed using immunohistochemistry. Cell proliferation was analyzed using the alamar blue proliferation assay. Induction of apoptosis was analyzed using the TUNEL assay and quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted human pancreatic tumors. Thirteen of 40 human pancreatic adenocarcinomas (32.5%) expressed LHRH receptors. We were able to show that treatment of LHRH receptor-positive MiaPaCa-2 and Panc-1 human pancreatic cancer cells with AEZS-108 (AN-152) resulted in apoptotic cell death in vitro. The antitumor effects could be confirmed in nude mice. AEZS-108 (AN-152) inhibited the growth of xenotransplants of human pancreatic cancers in nude mice significantly, without any apparent side effects. The cytotoxic LHRH agonist AEZS-108 (AN-152) seems to be a suitable drug for treatment of LHRH receptor-positive human pancreatic cancers with little toxicity.

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September 2011
Volume 26 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Gründker C, Ernst J, Reutter MD, Ghadimi BM and Emons G: Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers. Oncol Rep 26: 629-635, 2011.
APA
Gründker, C., Ernst, J., Reutter, M.D., Ghadimi, B.M., & Emons, G. (2011). Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers. Oncology Reports, 26, 629-635. https://doi.org/10.3892/or.2011.1340
MLA
Gründker, C., Ernst, J., Reutter, M. D., Ghadimi, B. M., Emons, G."Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers". Oncology Reports 26.3 (2011): 629-635.
Chicago
Gründker, C., Ernst, J., Reutter, M. D., Ghadimi, B. M., Emons, G."Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers". Oncology Reports 26, no. 3 (2011): 629-635. https://doi.org/10.3892/or.2011.1340