Concentration-dependent effects of a selective estrogen receptor modulator raloxifene on proliferation and apoptosis in human uterine leiomyoma cells cultured in vitro.
BACKGROUND
This study was conducted to elucidate the effects of raloxifene on proliferation and apoptosis in cultured human uterine leiomyoma cells.


METHODS
The monolayer cultures were treated with graded concentrations (10(-9), 10(-8) and 10(-7) M) of raloxifene and 10(-7) M 17beta-estradiol (E(2)). Cell viability, percentage of proliferating cell nuclear antigen (PCNA)-positive cells, percentage of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labelling (TUNEL)-positive cells and the expression of PCNA and Bcl-2 proteins were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay, immunocytochemistry, TUNEL assay and western blot analysis, respectively.


RESULTS
Compared with untreated cultures, the number of viable cultured cells, percentage of PCNA-positive cells and PCNA protein expression were significantly decreased by treatment with 10(-9) M raloxifene, but increased by treatment with either 10(-8) M or 10(-7) M raloxifene. In contrast, the percentage of TUNEL-positive cells was significantly increased and Bcl-2 protein expression was significantly decreased by treatment with 10(-9) M raloxifene, whereas they were not affected by treatment with either 10(-8) or 10(-7) M raloxifene.


CONCLUSIONS
In cultured leiomyoma cells, low concentration (10(-9) M) of raloxifene may inhibit the growth of leiomyoma cells, whereas high concentrations (10(-8) M, 10(-7) M) of raloxifene may promote their growth.
Liu
Jin
J
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Matsuo
Hiroya
H
Xu
Qin
Q
Chen
Wei
W
Wang
Jiayin
J
Maruo
Takeshi
T
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007889:Leiomyoma / Q000503:physiopathology; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000503:physiopathology
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol