关键词: 雌二醇, 子宫内膜癌, AKT, 增殖

Abstract:

Background and purpose: The occurrence of endometrial cancer may be related to the persistent stimulus of endogenous and exogenous estrogen without progesterone antagonist. But how does estrogen regulate cell proliferation is still unknown. AKT pathway is the most important signal transduction way to mediate proliferation in the cells. The main aim was to study whether estradiol induces the expression of VEGF, bFGF and IL-8 in the endometrial cancer HEC-1A cells by activating AKT, and its effect on proliferation. Methods: Western blot was used to detect the expression of AKT protein in HEC-1A cells after estradiol stimulation, AKT inhibitor or ER inhibitor stimulation followed by estradiol. Real-time PCR and ELISA were used to detect the gene and protein expression of VEGF, bFGF and IL-8 in different inhibitors. Cell colony formation assay, flow cytometry and CFSE assay were used to examine the proliferation in HEC-1A cells. Results: The expression of p-AKT protein in HEC-1A cells after stimulation with estradiol was markedly higher than that in the control group (P=0.006 2); the expression of p-AKT protein in AKT inhibitor group and ER inhibitor group were significantly decreased than that in estradiol group (P=0.006 0, P=0.006 4). qPCR and ELISA showed the mRNA and protein expression of VEGF, bFGF, IL-8 in estradiol group were significantly increased than that in control group (P<0.05); The expressions of VEGF, bFGF, IL-8 in AKT inhibitor group and ER inhibitor group were significantly decreased than that in estradiol group (P<0.01). The abilities of proliferation and cell cycle were significantly increased in HEC-1A cells after estradiol stimulation. Conclusion: Estrogen induces the production of VEGF, bFGF and IL-8 through activating AKT signal pathway.

Key words: Estrogen, Endometrial cancer, AKT, Proliferation