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Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells

Authors :
Gabor Halmos
Andrea Papadia
Elmar Aigner
Frank Köster
Luca Szalontay
Stefan Buchholz
Ferenc G. Rick
Florian Hohla
Christian Datz
Stephan Seitz
Andrew V. Schally
Awtar Krishan
Source :
Cancer Letters. 294:35-42
Publication Year :
2010
Publisher :
Elsevier BV, 2010.

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.

Details

ISSN :
03043835
Volume :
294
Database :
OpenAIRE
Journal :
Cancer Letters
Accession number :
edsair.doi.dedup.....41667802afb920cd4a9079a419e1513d
Full Text :
https://doi.org/10.1016/j.canlet.2010.01.018