Receptors for luteinizing hormone releasing hormone (LHRH) expressed in human non-Hodgkin's lymphomas can be targeted for therapy with the cytotoxic LHRH analogue AN-207.
We determined by immunohistochemistry the presence of LHRH receptors in surgical specimens of human non-Hodgkin's lymphomas (NHL) and investigated the expression of LHRH receptors in two human NHL cell lines, RL and HT by RT-PCR, Western blot and radioligand binding studies. In in vivo experiments with nude mice bearing tumours of these NHL cell lines, the efficacy of cytotoxic LHRH analogue AN-207 and its cytotoxic radical AN-201 was examined. LHRH receptors were detected in 94.1% of the human NHL specimens and in both NHL cell lines. AN-207 significantly (P < 0.01) inhibited the growth of RL and HT tumours, while the non-targeted AN-201 had no effects. Blockade of the LHRH receptors with an excess of LHRH agonist Decapeptyl suppressed the antitumour effects of AN-207. Our findings indicate that LHRH receptors expressed in a high percentage of human NHL specimens can be used for effective targeted therapy with the cytotoxic LHRH analogue AN-207.
Keller
Gunhild
G
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido St., New Orleans, LA 70112-1262, USA.
Schally
Andrew V
AV
Gaiser
Timo
T
Nagy
Attila
A
Baker
Benjamin
B
Halmos
Gabor
G
Engel
Jörg B
JB
D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007970:Leukopenia / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss
D012333:RNA, Messenger; D011966:Receptors, LHRH; C104648:AN 207; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin