雌二醇与不同孕激素联合对人乳腺癌细胞增殖的影响

目的探讨雌二醇/孕激素联合方案对人乳腺癌细胞MCF-7和MCF-7/PGRMC1(WT-12)增殖的影响。方法 MCF-7细胞,用表达PGRMC1的质粒稳定转染到MCF-7细胞,使其成为MCF-7/WT-12乳腺癌细胞。雌二醇浓度(10-10M,10-12M,10-14M)与孕酮、合成孕激素安宫黄体酮、炔诺酮序贯联合加入上述两种人乳腺癌细胞进行培养6天,MTT法分别测定MCF-7、MCF-7/WT-12肿瘤细胞的生长增殖情况。结果单纯雌二醇在高浓度10-10M下,明显刺激细胞生长,这种生长不受加入各种孕激素的影响。单纯雌二醇在低浓度下10-12M、10-14M下对MCF-7及MCF-7/WT-12细胞刺激增殖作用轻微或没有明显刺激细胞增殖的作用,然而,加用炔诺酮则可激发细胞明显的增殖反应,而增加安宫黄体酮和孕酮则显示中性作用,无激发反应。MCF-7/WT-12细胞的增殖反应更明显。结论雌二醇在表达孕激素受体膜组分1(progesterone receptor membrane component 1,PGRMC1)的MCF-7细胞中能明显诱发细胞增殖的增加,且表现为剂量依赖性。在低的雌二醇浓度下,某些孕激素可能启动了一种强增殖信号。关于HRT低剂量雌二醇致乳腺癌风险增加的可能性,可能与用某些特殊的孕激素有关。

The influence of estradiol/progestogen combinations on MCF-7 and MCF-7/PGRMC1 breast cancer cells proliferation

Objective To investigate the effect of estradiol/progestogen combinations on MCF-7 and MCF-7 breast cancer cells overexpressing progesterone receptor membrane component 1(PGRMC1).Methods MCF-7 cells were stably transfected with PGRMC1 expression plasmid(MCF-7/PGRMC1-3HA).Estradiol(10-10M,10-12M,10-14M) was sequentially combined with progesterone(P10-7M) or the synthetic progestins medroxyprogesterone acetate(MPA 10-7M),and norethisterone(NET 10-7M).Cell proliferation was investigated in MCF-7 and MCF-7/WT-12 cells.Results In sequential combination,E2 alone elicited a significant proliferative increase at 10-10M.This increase was not significantly influenced by the addition of the various progestogens.However,E2 alone at the lower concentrations of 10-12M and 10-14M showed no significant effect or slight increased effects on the proliferation of MCF-7 and MCF-7/WT-12 cells,whereby addition of NET triggered a significant proliferative response,in contrast P and MPA were neutral in this action,i.e.elicited no effect,this effect of proliferation is much more significant on MCF-7/WT-12 cells in contrast on MCF-7 cells.Conclusion Estradiol dose-dependently elicited a strong proliferative increase in MCF-7 cells overexpressing progesterone receptor membrane component 1(PGRMC1).At lower concentrations of estradiol,certain progestogens were able to trigger a strong proliferative signal.Concerning the possible increase of breast cancer risk during hormone therapy caused by low estradiol dosages,the use of specific progestogens might be of crucial relevance.