Effect of estrogen receptor antagonist on proliferation of human endometrioid carcinoma Ishikawa cells and its possible mechanism

Objective: To investigate the effects of estrogen receptor (ER) antagonists tamoxifen (TAM) and fulvestrant (ICI-182780) on the proliferation of highly differentiated human endometrioid carcinoma Ishikawa cells, and to explore the possible mechanism. Methods: Ishikawa cells were cultured in vitro, and treated with ER antagonist TAM alone, ICI-182780 alone, β-estradiol alone, TAM combined with β-estradiol, ICI-182780 combined with β-estradiol, respectively; while Ishikawa cells were not treated with any drugs as the control. The cell proliferation was detected by MTT method. The changes of cell morphology were observed under a light microscope and an electron microscope, respectively. The expression levels of p57kip2 and cyclin E mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Results: Compared with the control group, the proliferation ability of Ishikawa cells in TAM group was lightly enhanced (P > 0.05), while those in the other groups were decreased (all P < 0.05). Compared with β-estradiol group, the proliferation abilities of Ishikawa cells in TAM group and β-estradiol+TAM group were increased (both P < 0.05), while those in ICI-182780 group and β-estradiol+ICI-182780 group were weakened (both P < 0.05). Compared with the control group, the cell density in β-estradiol+ICI-182780 group was reduced, while there was no obvious change in the other groups; the microvilli on the cell surface were reduced in each experimental group. The slight swelling of endoplasmic reticulum was seen in TAM group and β-estradiol group, and the moderate swelling of partial endoplasmic reticulum was seen in ICI-182780 group, while the most of endoplasmic reticulum and mitochondria had significant swelling in β-estradiol+TAM group and β-estradiol+ICI-182780 group and the autophagy increased. Compared with the control group, the expressions of p57kip2 mRNA and protein were decreased, while the expressions of cyclin E mRNA and protein were increased in the TAM group; but in other groups, the expressions of p57kip2 mRNA and protein were increased, while the expressions of cyclin E mRNA and protein were decreased. Compared with β-estradiol group, the expressions of p57kip2 mRNA and protein were increased in ICI-182780 group and β-estradiol+ICI-182780 group, while the expressions of cyclin E mRNA and protein were decreased; but in TAM group and β-estradiol+TAM group, the expressions of p57kip2 mRNA and protein were decreased, while the expressions of cyclin E mRNA and protein were increased. Conclusion: ICI-182780 can restrain the proliferation of Ishikawa cells, while TAM slightly promotes the proliferation of Ishikawa cells. The effects of ICI-182780 and TAM on endometrioid carcinoma are not completely consistent. This may be related to ICI-182780 can up-regulate the expression of the anti-oncogene p57kip2 and down-regulate the expression of the oncogene cyclin E, TAM can slightly down-regulate the expression of p57kip2 and up-regulate the expression of cyclin E. ICI-182780 may be more suitable for individual endocrine therapy of the patients with endometrioid carcinoma than TAM. DOI:10.3781/j.issn.1000-7431.2018.11.170