人乳腺癌细胞增殖实验检测典型雌激素复合效应

目的 研究4种典型雌激素17β雌二醇(E2)、乙炔雌二醇(EE2)、雌三醇(E3)、雌酮(E1)复合作用对人乳腺癌细胞(MCF-7)乳腺癌增殖效应的影响,并比较独立作用模型(IA模型)和浓度加和模型(CA模型)对雌激素复合效应评价的优劣.方法 选用E2+EE2、E2+E3和E2+E1两类雌激素物质的联合组合设计,噻唑蓝(MTT)法检测MCF-7细胞增殖效应.结果 E2在10-9mol/L最大增殖效应为325.48%,EE2在10-9 mol/L最大增殖效应为330.34%,E3在10-9 mol/L最大增殖效应为255.22%,E1在10-9 mol/L最大增殖效应为199.61%;E2+EE2、E2+E3、E2+E1 3组摩尔浓度配比下IA模型拟合结果与实验结果十分接近,IA模型往往高估实验结果,而CA模型往往低估实验结果;除EC(E2,30)+C(EE2,70)这组结果超过E2所表现出的最大雌激素效应(即效应比小于1)外,其中各组结果均弱于E2表现出的最大增殖效应.结论 4种受试物雌激素效应依次为EE2>E2>E3>E1;IA模型对二元混合物复合效应的预测结果优于CA模型;二元混合物表现出的协同作用比例较小.

Combined effects of typical natural estrogens with MCF-7 proliferation assay

Objective To study 17 β-estradiol(E2). ethinylestradiol(EE2),estriol(E3),estrone (E1) on MCF-7 proliferation effects, and compare the effects of independent action (IA) model with concentration addition (CA) model in assessing the combined effects of estrogen. Methods The combinations of E2+EE2,E2+E3 and E2+E1 were chosen and the cellular proliferation effects were examined by MTT assay. Results The maximum proliferation effects at dose of 10-9 mol/L were 325.48% for E2, 330.34% for EE2, 255.22% for E3, and 199.61% for E1. In the E2+EE2, E2+E3, E2+E1 groups, the results of IA model analysis were very close to the experimental results. The IA model tended to overestimate the experimental results, while the CA model often underestimated the experimental results. In the EC (E2,30)+C (EE2,70) group, the results exceeded the maximum estrogen effects of E2, while in other groups, the results were lower. Conclusions The estrogenic effects of the four tested substances from high to low efficiency are EE2>E2>E3>E1. The effect of IA model in predicting the combined effects of binary mixture is better than CA model. A small proportion of binary mixture shows synergy.