Powerful Inhibition of Experimental Human Pancreatic Cancers by Receptor Targeted Cytotoxic LH-RH analog AEZS-108

Authors

Karoly Szepeshazi, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education
Andrew V. Schally, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education; University of Miami
Norman L. Block, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education; University of Miami
Gabor Halmos, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education; University of Miami; University of Debrecen
Mehrdad Nadji, University of Miami
Luca Szalontay, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education
Irving Vidaurre, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education
Andrew Abi-Chaker, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education; University of Miami
Ferenc G. Rick, Veterans Affairs Medical Center; South Florida VA Foundation for Research and Education; Herbert Wertheim College of Medicine, Florida International University

Date of this Version

6-3-2013

Document Type

Article

Abstract

Pancreatic carcinoma is one of the cancers with the worse prognosis, thus any therapeutic improvement is imperative. Cytotoxic LH-RH analog, AN-152 (proprietary designation, AEZS-108), consisting of doxorubicin (DOX) conjugated to D-Lys6LH-RH, is now in clinical trials for targeted therapy of several sex hormone-dependent tumors that express LH-RH receptors. We investigated LH-RH receptors in human pancreatic carcinoma and the effects of AN-152 (AEZS-108) on experimental pancreatic cancers. We determined LH-RH receptor presence in human pancreatic cancer samples by immunohistochemistry and, in three human pancreatic cancer lines (SW-1990, Panc-1 and CFPAC-1), by binding assays and Western blotting. The effects of the cytotoxic LH-RH analog were investigated on growth of these same cancer lines xenografted into nude mice. We also analyzed differences between the antitumor effects of the cytotoxic analog and its cytotoxic radical alone, doxorubicin (DOX), on the expression of cancer-related genes by PCR arrays. LH-RH receptors were expressed in two randomly selected surgically removed human pancreatic cancer samples and in all three cancer lines. Cytotoxic LH-RH analogs powerfully inhibited growth of all three tumor lines in nude mice; AN-152 was significantly stronger than DOX on Panc-1 and CFPAC-1 cancers. PCR array showed that cytotoxic LH-RH analog AN-152 affected the expression of genes associated with cellular migration, invasion, metastasis and angiogenesis more favorably than DOX, however the changes in gene expression varied considerably among the three cancer lines. Cytotoxic LH-RH analog, AEZS-108, may be a useful agent for the treatment of LH-RH receptor positive advanced pancreatic carcinoma.

Originally Published In

Oncotarget

PMID

23744510

DOI

10.18632/oncotarget.1044

Recommended Citation

Szepeshazi, Karoly; Schally, Andrew V.; Block, Norman L.; Halmos, Gabor; Nadji, Mehrdad; Szalontay, Luca; Vidaurre, Irving; Abi-Chaker, Andrew; and Rick, Ferenc G., "Powerful Inhibition of Experimental Human Pancreatic Cancers by Receptor Targeted Cytotoxic LH-RH analog AEZS-108" (2013). All Faculty. 42.
https://digitalcommons.fiu.edu/all_faculty/42

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.