Growth dynamics of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated receptor-gamma ligand, pioglitazone.
Uterine leiomyomas (fibroids) are the most frequent tumour of the female reproductive tract and are the primary cause of hysterectomies in women worldwide. Effective treatment options are few. In a search for alternative treatments, we have established primary cultures of human leiomyoma cells and adjacent myometrial tissues, and documented their growth dynamics in response to estradiol (E2) and pioglitazone (PIO), a peroxisome proliferation-activated receptor-gamma (PPARgamma) ligand, currently in clinical use for type II diabetes mellitus. Human uterine primary cell cultures display morphology and desmin content consistent with their smooth muscle origin. Surprisingly, leiomyoma cells exhibited slower proliferation patterns relative to matched myometrial cells, both in the absence and presence of E2, suggesting that tumour genesis may not be because of increased growth potential but could be related to suppression of growth-inhibiting factors in vivo. PIO significantly inhibited the cell proliferation of both myometrial and leiomyoma cells in a dose-dependent manner. Our results suggest the possibility of using PPARgamma ligands, such as PIO, as therapeutic agents for the conservative management of uterine fibroids.
Loy
C J
CJ
Department of Obstetrics and Gynecology, National University of Singapore, Singapore.
Evelyn
S
S
Lim
F K
FK
Liu
M H
MH
Yong
E L
EL
D000328:Adult; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology*; D008024:Ligands; D008875:Middle Aged; D024510:Muscle Development / Q000502:physiology; D009215:Myometrium / Q000166:cytology / Q000254:growth & development; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone