Oxytocin inhibits the progression of human ovarian carcinoma cells in vitro and in vivo.
The neurohypophyseal nonapeptide oxytocin (OT) is involved in many biologic functions and regulation of cell proliferation under both physiologic and neoplastic conditions. In some cases, OT exhibits an oxytocin receptor (OTR)-mediated antiproliferative effect on cancer cells. In this study, we examined the effects of OT on ovarian carcinoma progression in vitro and in vivo. We investigated the inhibitory effects of OT on cell growth, invasion and migration in vitro. Furthermore, we examined the OT effects in vivo ovarian carcinoma model. We demonstrated OTR expressions in the large majority of ovarian carcinoma tissues, and OT inhibited not only proliferation but also migration and invasion in ovarian carcinoma cells in vitro. Furthermore, we examined the mechanisms of the antiinvasive ability of OT. Secretion of matrix metalloproteinase 2 was slightly inhibited by 10(-7) M OT, while treatment with 10(-7) M OT for 24 hr remarkably enhanced the expression of E-cadherin. In addition, our in vivo study showed that intraperitoneal administration of OT resulted in the reduction of intraperitoneal dissemination of ovarian carcinoma cells. Mean tumor burden in the OT-treated group (0.2 +/- 0.11 g) was significantly (p < 0.05) less than that of physiologic saline-treated group (0.5 +/- 0.54 g). This evidence implies that OT may functionally suppress peritoneal dissemination in ovarian carcinoma.
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takanori
T
Morita
Kiyosumi
K
Shibata
Fumitaka
F
Kikkawa
Hiroaki
H
Kajiyama
Kazuhiko
K
Ino
Shigehiko
S
Mizutani
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000637:transplantation
D015820:Cadherins; D018045:Receptors, Oxytocin; D010121:Oxytocin; D020778:Matrix Metalloproteinase 2