Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells.
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.
Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Paracelsusstrasse 37, Oberndorf, Austria.
Florian
F
Hohla
Stefan
S
Buchholz
Andrew V
AV
Schally
Awtar
A
Krishan
Ferenc G
FG
Rick
Luca
L
Szalontay
Andrea
A
Papadia
Gabor
G
Halmos
Frank
F
Koster
Elmar
E
Aigner
Christian
C
Datz
Stephan
S
Seitz
D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000814:Aniline Compounds / Q000627:therapeutic use*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000401:mortality; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000814:Aniline Compounds; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; C101130:somatostatin receptor type 1; C000956:N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; D013004:Somatostatin; D015078:2-Hydroxyphenethylamine; D004317:Doxorubicin; C094573:somatostatin receptor 5