ERK1/2及PI3K-Akt途径在雌激素促进人甲状腺未分化癌FRO细胞增殖中的作用及其机制

Role of ERK1/2 and PI3K-Akt Pathways in Promoting Proliferation of Human Anaplastic Thyroid Carinoma FRO Cells by Estrogen and Relevant Mechanism

目的探讨ERK1/2、PI3K-Akt途径在雌激素17β-雌二醇(17β-estradiol,E2)促进人甲状腺未分化癌FRO细胞增殖中的作用及其机制。方法分别用E2、雌激素受体抑制剂ICI182780(ICI)、ERK1/2抑制剂PD98059(PD)和PI3K-Akt抑制剂LY294002(LY)单独或联合处理FRO细胞,MTT法检测细胞增殖率,Western blot法检测细胞ERα、ERβ、Bcl-2及Bax蛋白的表达水平。结果 E2可促进FRO细胞增殖及ERα、Bcl-2蛋白的表达,抑制Bax蛋白的表达;ICI可抑制Bcl-2蛋白的表达,对Bax蛋白的表达无明显影响;PD和LY可抑制E2对FRO细胞的上述作用。结论 E2可通过激活ERK1/2、PI3K-Akt通路,增加Bcl-2/Bax的比值,促进FRO细胞增殖。

Objective To investigate the role of ERK1/2 and PI3K-Akt pathways in promoting the proliferation of human anaplastic thyroid carcinoma FRO cells by 17β-estradiol（E2）,an estrogen,as well as the relevant mechanism.Methods FRO cells were treated with E2,estrogen receptor inhibitor ICI182780（ICI）,ERK1/2 inhibitor PD98059（PD） and PI3K-Akt inhibitor LY294002（LY）,alone or in combination,then determined for proliferation rate by MTT method,and for expression levels of ERα,ERβ,Bcl-2 and Bax proteins.Results E2 promoted the proliferation of FRO cells and the expressions of ERα and Bcl-2 proteins while inhibited the expression of Bax protein.ICI inhibited Bcl-2 expression while showed no significant effect on Bax expression.However,both PD and LY inhibited the above-mentioned effects of E2 on FRO cells.Conclusion E2 promoted the proliferation of FRO cells by activating ERK1/2 and PI3K-Akt pathways and increasing the ratio of Bcl-2 to Bax.