The broad-spectrum chemokine inhibitor NR58-3.14.3 suppresses the implantation and survival of human endometrial implants in the nude mice endometriosis model.
Many chemokines likely contribute to the pathogenesis of endometriosis. The authors hypothesize that the broad-spectrum chemokine inhibitor NR58-3.14.3 may prevent ectopic human endometrium implantation and growth. After placing human endometrium fragments into the peritoneal cavity, ovariectomized athymic nude mice (n = 31) receiving intramuscular estradiol valerate were randomly assigned to daily intraperitoneal injections of either phosphate-buffered saline or NR58-3.14.3. Fourteen days later, the implant number and volume, proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) index, and MTT cell viability were assessed in the implants. NR58-3.14.3 reduced the total number (45%) and total volume (81%) of endometriotic lesions (P < .05) and revealed a lower PCNA and higher TUNEL index in ectopic implants compared with controls (P < .05). NR58-3.14.3 treatment did not affect endometrial cell proliferation in vitro. NR58-3.14.3, by possibly regulating cell survival, can reduce the number and size of ectopic implants in vivo, supporting the potential use of chemokine inhibitors in novel therapies for endometriosis.
Kayisli
Umit A
UA
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Berkkanoglu
Murat
M
Zhang
Lufang
L
Kizilay
Gulnur
G
Arici
Aydin
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000637:transplantation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011897:Random Allocation
D010456:Peptides, Cyclic; C411952:cyclo(cysteinyl-glutaminyl-isoleucyl-tryptophyl-lysyl-glutaminyl-lysyl-prolyl-aspartyl-leucyl-cysteinyl-amide)