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.
Hohla
Florian
F
Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Paracelsusstrasse 37, Oberndorf, Austria.
Buchholz
Stefan
S
Schally
Andrew V
AV
Krishan
Awtar
A
Rick
Ferenc G
FG
Szalontay
Luca
L
Papadia
Andrea
A
Halmos
Gabor
G
Koster
Frank
F
Aigner
Elmar
E
Datz
Christian
C
Seitz
Stephan
S
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