摘要
目的研究孕激素受体膜组分1 (progesterone receptor membrane component 1,PGRMC1)对激素诱导的乳腺癌细胞的促增生作用,采用单用雌二醇(estradiol,E2)/周期序贯(sequential combination)/连续联合(continuous combination)不同的治疗方案,观察其对乳腺癌细胞增生的影响。方法采用脂质体转染法将T47D稳定转染后,对转染空质粒(T47D-HA-vector)或转染PGRMC1(T47D-HA-PGRMC1)的T47D乳腺癌细胞系,分别用E2(0. 1、0. 01、0. 001 nmol/L),或周期序贯/连续联合方案刺激6 d后,采用CCK-2法检测乳腺癌细胞的增生。结果单用E2(0. 1、0. 01、0. 001 nmol/L),T47D-HA-vector细胞未出现明显增生(P> 0. 05),T47D-HA-PGRMC1在E2浓度为0. 1 nmol/L时与对照组(56%,P <0. 05)及与T47D-HA-vector(36%,P <0. 05)比均出现明显增加的细胞增生;周期序贯方案,T47D-HA-PGRMC1在E2/炔诺酮(norethisterone,NET)(E2=0. 001 nmol/L)刺激时与对照组(82%,P <0. 05)及与T47D-HA-vector(63%,P <0. 05)比均显著地促进细胞增生。T47D-HA-vector在E2/NET(E2=0. 1nmol/L)刺激时与对照组相比显著地促进细胞增生(37%,P <0. 05),T47D-HA-PGRMC1在E2/屈螺酮(drospirenone,DRSP)或E2/NET(E2=0. 1 nmol/L)刺激时与对照组(105%,170%,P <0. 05)及与T47D-HA-vector(84%,133%,P <0. 05)比均显著地促进细胞增生;采用连续联合方案时,T47D-HA-PGRMC1在E2/DRSP或E2/NET(E2=0. 001 nmol/L)刺激时与对照组(77%,158%,P <0. 05)及与T47D-HA-vector(60%,136%,P <0. 05)比均显著地促进细胞增生。T47D-HA-vector在E2/NET(E2=0. 1nmol/L)刺激时与对照组相比显著地促进细胞增生(44%,P <0. 05),T47D-HA-PGRMC1在E2/DRSP或E2/NET(E2=0. 1 nmol/L)刺激时与对照组(129%,174%,P <0. 05)及与T47D-HA-vector(97%,131%,P <0. 05)比均显著地促进细胞增生。结论PGRMC1能够明显促进周期序贯/连续联合方案诱导的乳腺癌增生,与周期序贯方案相比,连续联合方案对T47D增生的促进作用更加明显。
Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)on the risk of hormone induced breast cancer,and compare the effects of different treatment regimens:estradiol(E2)/sequential combination/continuous combination(E2/DRSP、E2/NET)on breast cancer proliferation.Methods After stabilized transfection by lipofection,T47 D cells transfected with vector(T47 D-HA-vector)or PGRMC1(T47 D-HA-PGRMC1)were stimulated with E2 alone(0.1,0.01,0.001 nmol/L),or sequential/continuous combination.CCK-2 method was performed to measure cell proliferation.Results When treated with E2(0.001,0.01,0.1 nmol/L)alone,T47 D-HA-vector cells did not show significant proliferation(P>0.05).At concentration of 0.1 nmol/L,T47 D-HA-PGRMC1 cell reached a significant increase in cell proliferation compared with the control group(56%,P<0.05)and compared with T47 D-HA-vector group(36%,P<0.05);when treated with sequential combination,T47 D-HA-PGRMC1 cell under E2/NET treatment(E2=0.001 nmol/L)showed a significant increase in cell proliferation compared with the control group(82%,P<0.05)and T47 D-HA-vector group(63%,P<0.05).Under the same stimulation,when the concentration of E2 reached 0.1 nmol/L,T47 D-HA-vector showed a significant increase compared with the control group(37%,P<0.05),and for the T47 D-HA-PGRMC1 cell line,when under E2/drospirenone(DRSP)or E2/norethisterone(NET)stimulation(E2=0.1 nmol/L),a significant increase compared with the control group(105%,170%,P<0.05)and T47 D-HA-vector group(84%,133%,P<0.05)was observed;when treated with the continuous combination,the T47 D-HA-PGRMC1 cell line showed a significant increase in cell proliferation under E2/DRSP or E2/NET stimulation(E2=0.001 nmol/L)compared with the control group(77%,158%,P<0.05)and T47 D-HA-vector group(60%,136%,P<0.05).The T47 D-HA-vector cell line showed a significant increase under E2/NET stimulation(E2=0.1 nmol/L)compared with the control group(44%,P<0.05),and the T47 D-HA-PGRMC1 cell line under E2/DRSP or E2/NET stimulation(E2=0.1 nmol/L)s
作者
李雪
阮祥燕
谷牧青
蔡桂举
赵越
Alfred O.Mueck
Li Xue;Ruan Xiangyan;Gu Muqing;Cai Guiju;Zhao Yue(Department of Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China;Department for Women's Health,University Women's Hospital and Research Center for Women's Health,University of Tuebingen,Tuebingen D-72076,Germany)
出处
《首都医科大学学报》
CAS
北大核心
2019年第2期237-243,共7页
Journal of Capital Medical University
基金
国家自然科学基金(81671411)
北京市自然科学基金(7162062)
北京市科技新星交叉项目(Z161100004916045)
北京市卫生系统高层次卫生技术人才(学科带头人)(2014-2-016)
北京市医院管理局登峰计划(DFL20181401)
首批北京市级妇幼保健专科示范单位"更年期保健专科"(2018.01-2020.12)~~
关键词
研究孕激素受体膜组分1
周期序贯方案
连续联合方案
乳腺癌
细胞增生
progesterone receptor membrane component 1
sequential combination
continuous combination
breast cancer
cell proliferation
