Studies On The Effect And Mechanisms Of Tamoxifen On Endometrium

Objective: The study was conducted to investigate the effects of tamoxifen(TAM)on rat's endometria of bilateral ovariectomy and sham surgery, and on the cell lines of MCF-7,ISK and Hela. It maybe provide theory to elucidate the possible mechanism of TAM induced endometrium pathogenesis, and program to prevent and therapy pathological change of endometrium.Methods: Some methods, Light microscope and transmission electron microscopeobserved rat endometrium, immunohistochemistry,tunnel and Westen blot determined affection TAM on endometrium, were used in the study in vivo. The other methods, MTT,immunofluorescence and flow cytometry, were also used to examine affection of TAM on MCF-7 cell,ISK cell and Hela cell in vitro.Results: 1,Some toxicities were found for rat in dose of TAM 50 mg·kg^-1 ig for 28days continuesly, including lose body weight,lipsotrichia and pathological changes of endumetria. 2,In ovariectomized rat group, TAM increased uterus weight and uterus to body weight ratio, and increased serum estrogen level. In sham group, TAM decreased uterus weight and uterus to body weight ratio, and decreased serum estrogen level. At two groups, TAM reduced the expression of uterus Erβand serum progesterone level, and elevated the expression of uterus PR. 3,After TAM administration, a slight indication showed that the positive cells of PCNA was fewer in sham group than control and that was more in ovariectomized group. Apoptosis cell significantly decreased compared with control group respectively. 4,TAM was able to inhibit cell proliferation for MCF-7and facilitate proliferation for ISK cell and Hela cell, but at the letter cells TAM could inhibit proliferation when lower than a micromolecular concentration. TAM could induce apoptosis of MCF-7 cell and slight inhibit apoptosis of ISK cell. TAM could depress the expression of bcl-2 and increase the expression of bax in the MCF-7. The result was contrary in the ISK cell and Hela cell.Conclusions: 1,TAM was able to induce the pathological changes of ratendometrium and some toxicological reaction after 50 mg·kg^-1 ig 28 days continuesly. 2,TAM expressed twofold effects in deffrent serum estrogen level. TAM had the estrogen-like effect on endometrium in low estrogen and antiestrogen effect in high estrogen. 3,Main action of TAM was not stimulated endometrium proliferation, but inhibit endometrium apoptosis. 4,TAM had different effects on tumor cells of MCF-7,ISK and Hela. TAM influence proliferation and apoptosis by change oncogene and anti-oncogene.