The Effects Of Tamoxifen On Proliferation In Vitro In Human Endometrial Carcinoma Cells

Objective As a choice drug in the endocrine therapy of breast cancer inpremenopausal and postmenopausal women, it is used widely in clinic. Itcan degrade the recurrence rate and mortality obviously. While TAMcause proliferation lesion in endometria after long-term use, evenincrease the incidence of endometrial carcinoma. Thus, it is important toexplore the effect and mechanism of TAM on human endometrial, in orderto guide the clinical utilization of TAM safely and reasonably. Toinvestigate the effects of TAM on the proliferation of Ishikawa humanendometrial carcinoma cells and the effects of 17β-E₂ and TAM+17β-E₂on the proliferation of Ishikawa cells, the distribution of cell cycle phaseand the expression of C-myc, Bcl-2, Bax. Explore the mechanisms of TAMincreasing the incidence of endometrial carcinoma and supply newenlightment and experimental basis in directing the safety and reasonableuse of TAM to prevent and cure the endometrial carcinoma.Methods The proliferation of Ishikawa cells were induced by TAM indifferent concentrations for 24, 48, 72, 96 hours separately and applyMTT assay to observe the effect. Then Ishikawa cells were treated withTAM, 17β-E₂ and TAM+17β-E₂ for different time, applying MTT assay,flow cytometer and immunocytochemistry method to observe the cellproliferation rate, the distribution of cell cycle phase and the change ofexpressions of C-myc, Bcl-2, Bax.Results TAM promoted the proliferation of Ishikawa cells with lowdose, on the contrary, TAM inhibited the proliferation of Ishikawa cellswith high dose. All experimental group could promote the proliferation ofIshikawa cells at different time, but the proliferation rate of Ishikawacells with 17β-E₂ or TAM+17β-E₂ was higher than that of Ishikawacells with TAM. The proportion of G₀/G₁ phase in cell cycle declined while S phase heightened in all experimental group compared withcontrol group. Compared to group T and group TE, the proportion ofG₀/G₁ phase in group E declined (P＜0.05), while S phase heightened (P＞0.05); the proportion of G₀/G₁ phase in group TE was lower than thatin group T (P＞0.05), while the proportion of S phase in group TE washigher than group T (P＞0.05). Different experimental group couldup-regulate the expression of C-myc and Bcl-2, while down regulate theexpression of Bax for 24 hours. The masculine expression rate of C-myc,Bcl-2 in group E or group TE was higher than group T, while themasculine expression rate of Bax was lower than it.Conclusions 1,TAM promoted the proliferation of Ishikawa cells withlow dose, on the contrary, TAM inhibited the proliferation of Ishikawacells with high dose. It may be related to the TAM's cytotoxicity. Theconsequence hints that the effect of TAM promoting proliferation hasdependence in certain dosage range.2,TAM, 17β-E₂ and TAM+17β-E₂ could promote the proliferation ofIshikawa cells at different time. The proliferation rate of Ishikawa cells ingroup E and TE is higher than group T, and the proliferation rate ofIshikawa cells in group E is higher than group TE. It hints that TAM hasweek estrogenic effect and can promote the proliferation of Ishikawa cells,which may be mediated by ER, also it has another proliferationmechanism that is different with17β-E₂.3,Similar to 17β-E₂, TAM can decline the proportion of G₀/G₁ phase incell cycle while heighten S phase. It might through some pathway to makemore cells through checkpoint G₁/S into S phase, and synthesis DNA,then promote cell proliferation.4,TAM also might up-regulate the expression of C-myc, to promoteproliferation and inhibit differentiation and apoptosis. Furtherup-regulate the expression of Bcl-2, and indirectly down-regulate the expression of Bax to promote the proliferation of Ishikawa cells.