Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells |
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| Authors: | Florian Hohla Stefan Buchholz Andrew V. Schally Awtar Krishan Ferenc G. Rick Luca Szalontay Andrea Papadia Gabor Halmos Frank Koster Elmar Aigner Christian Datz Stephan Seitz |
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| Affiliation: | 1. Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Paracelsusstrasse 37, 5110 Oberndorf, Austria;2. Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, 1201 N.W. 16th Street, Miami, FL 33125, USA;3. Department of Pathology and Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, 1800 N.W. 10th Ave, Miami, FL 33136, USA;4. Department of Gynecology and Obstetrics, University of Regensburg, Landshuterstrasse 65, 93057 Regensburg, Germany;5. Department of Biopharmacy, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary;6. Department of Gynecology and Obstetrics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany |
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| Abstract: | ![]()
The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and high affinity binding sites for SST were detected in all CRC cell lines and in P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In vivo, AN-162 reduced the volume of CRC xenografts more effectively than its unconjugated components. Our results suggest that AN-162 inhibits growth of experimental CRC more effectively than DOX and increases sensitivity of DOX resistant human leukemia cells. |
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| Keywords: | SST, somatostatin DOX, doxorubicin CRC, colorectal cancer MDR, multiple drug resistance MTS, 3-(45-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium TopII, Topoisomerase II Pgp, P-glycoprotein MRP-1, MDR related protein-1 |
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