Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells.
BACKGROUND
Metformin, a widely used treatment for diabetes that improves insulin sensitivity, also has both antiinflammatory properties and a modulatory effect on ovarian steroid production, two actions that have been suggested to be efficacious in therapy for endometriosis.


OBJECTIVE
To determine whether metformin may be effective for the treatment of endometriosis, we evaluated the effects of this agent on inflammatory response, estradiol production, and proliferation of endometriotic stromal cells (ESCs).


METHODS
ESCs derived from ovarian endometriomas were cultured with various concentrations of metformin.


METHODS
IL-8 production, mRNA expression and aromatase activity, and 5-bromo-2'-deoxyuridine incorporation in ESCs were measured.


RESULTS
Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP-induced mRNA expression and aromatase activity, and 5-bromo-2'-deoxyuridine incorporation in ESCs.


CONCLUSIONS
These results suggest that further investigation into the unique therapeutic potential of metformin as an antiendometriotic drug is warranted.
Takemura
Yuri
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Yoshino
Osamu
O
Hasegawa
Akiko
A
Hirata
Tetsuya
T
Hirota
Yasushi
Y
Nose
Emi
E
Morimoto
Chieko
C
Harada
Miyuki
M
Koga
Kaori
K
Tajima
Toshiki
T
Yano
Tetsu
T
Taketani
Yuji
Y
D000328:Adult; D000963:Antimetabolites; D001141:Aromatase / Q000378:metabolism*; D015415:Biomarkers; D001973:Bromodeoxyuridine; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004715:Endometriosis / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*
D000963:Antimetabolites; D015415:Biomarkers; D004967:Estrogens; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D008687:Metformin; D007770:L-Lactate Dehydrogenase; D001141:Aromatase; D001973:Bromodeoxyuridine