他莫昔芬治疗转染孕激素受体膜组分1乳腺癌裸鼠模型对乳腺肿瘤组织Ki-67表达的影响

doi:10.3969/j.issn.1006-7795.2019.04.008

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (4): 533-538.doi: 10.3969/j.issn.1006-7795.2019.04.008

他莫昔芬治疗转染孕激素受体膜组分1乳腺癌裸鼠模型对乳腺肿瘤组织Ki-67表达的影响

张凌燕¹, 阮祥燕¹, 蔡桂举¹, 谷牧青¹, Alfred O. Mueck^1,2

1. 首都医科大学附属北京妇产医院内分泌科, 北京 100026;
2. 德国图宾根大学妇产医院妇女健康部与妇女健康研究中心, 图宾根 D-72076, 德国

收稿日期:2019-05-25 出版日期:2019-07-21 发布日期:2019-07-19
通讯作者: 阮祥燕 E-mail:ruanxiangyan@163.com
基金资助:
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），北京市医院管理局登峰计划（DFL20181401），北京市卫生系统高层次卫生技术人才（2014-2-016），首批北京市级妇幼保健专科示范单位"更年期保健专科"。

Effect of tamoxifen on Ki-67 expression in breast tumor tissue of nude mice transfected with progesterone receptor membrane component 1

Zhang Lingyan¹, Ruan Xiangyan¹, Cai Guiju¹, Gu Muqing¹, Alfred O. Mueck^1,2

1. Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
2. Department for Women's Health, University Women's Hospital and Research Center for Women's Health, University of Tuebingen, Tuebingen D-72076, Germany

Received:2019-05-25 Online:2019-07-21 Published:2019-07-19
Supported by:
This study was supported by National Natural Science Foundation of China (81671411), Natural Science Foundation of Beijing (7162062), Beijing Nova Program Interdisciplinary Cooperation Projects (Z161100004916045), Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20181401),Beijing Municipality Health Technology Highlevel Talent (2014-2-016), First Batch of Demonstration Units of Maternal and Child Health Specialty at Beijing Level "Climacteric Health Specialty".

摘要/Abstract

摘要： 目的探讨他莫昔芬（tamoxifen，TAM）对转染孕激素受体膜组分1（progesterone receptor membrane component 1，PGRMC1）乳腺癌模型MCF-7乳腺肿瘤组织增生指数Ki-67表达的影响及其作用机制。方法乳腺癌MCF-7细胞进行培养、孵育及传代后转染含有PGRMC1（MCF-7-HA-PGRMC1）或空质粒（MCF-7-HA-vector），去势小鼠（共48只）包埋雌激素（estradiol，E2）缓释片48 h后，然后分别将以上两种细胞接种至裸鼠，作为实验组及对照组。每组再分别用安慰剂、黄体酮、他莫昔芬、他莫昔芬联合黄体酮处理，种瘤56 d后实施安乐死，无菌操作下完整摘除肿瘤组织，免疫组织化学法检测荷瘤体中Ki-67表达情况。结果实验组肿瘤组织中Ki-67表达较对照组升高（P<0.001），差异有统计学意义；实验组中，与单独E2相比，E2+TAM可降低肿瘤组织中Ki-67的表达，差异有统计学意义（P<0.001）；而E2+黄体酮并未促进Ki-67的表达（P>0.05）。与E2相比，E2+黄体酮+TAM组肿瘤组织中Ki-67的表达明显降低，差异有统计学意义（P<0.001）。结论 PGRMC1可增加Ki-67表达、加快细胞增生，他莫昔芬治疗后可通过降低Ki-67表达拮抗PGRMC1导致的乳腺肿瘤细胞增生。

关键词: 他莫昔芬, 孕激素受体膜组分1, 乳腺癌模型, Ki-67

Abstract: Objective To investigate the effect of tamoxifen (TAM) on the expression of proliferative index Ki-67 in breast cancer tissue of MCF-7 breast cancer model transfected with progesterone receptor membrane component 1 (PGRMC1) and its mechanism. Methods MCF-7 cells of breast cancer were cultured, incubated and subcultured, transfected with PGRMC1 (MCF-7-HA-PGRMC1) or empty plasmid (MCF-7-HA-vector), and then they were inoculated into randomly grouped castrated nude mice, including experimental group and control group. Estradiol (E2) sustained release tablets were embedded in 48 castrated nude mice for 48h,then the above two kinds of cells were inoculated into nude mice as experimental group and control group respectively. Additionaly placebo, progesterone, tamoxifen, tamoxifen and progesterone were administrated to each group. After 56 days of implantation, euthanasia was performed. Breast tumor tissues were removed completely under aseptic operation and Ki-67 expression was detected with immunohistochemistry. Results Ki-67 expression in tumor tissues of the experimental group significantly increased compared with that of the control group (P<0.001). In the experimental group, compared E2, E2+TAM combined therapy could reduce the expression of Ki-67 in tumor tissues, with statistically significant difference (P<0.001). However, E2 + progesterone did not promote the expression of Ki-67 (P>0.05). The expression of Ki-67 in E2+progesterone+TAM group significantly lower than that in estradiol +alone (P<0.001). Conclusion PGRMC1 increased the expression of Ki-67 and accelerate cell proliferation. Tamoxifen therapy antagonized pgrmc1-induced proliferation of breast tumor cells by reducing the expression of Ki-67.

Key words: tamoxifen, progesterone receptor membrane component 1 (PGRMC1), breast cancer model, Ki-67

中图分类号:

R711

张凌燕, 阮祥燕, 蔡桂举, 谷牧青, Alfred O. Mueck. 他莫昔芬治疗转染孕激素受体膜组分1乳腺癌裸鼠模型对乳腺肿瘤组织Ki-67表达的影响[J]. 首都医科大学学报, 2019, 40(4): 533-538.

Zhang Lingyan, Ruan Xiangyan, Cai Guiju, Gu Muqing, Alfred O. Mueck. Effect of tamoxifen on Ki-67 expression in breast tumor tissue of nude mice transfected with progesterone receptor membrane component 1[J]. Journal of Capital Medical University, 2019, 40(4): 533-538.

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他莫昔芬治疗转染孕激素受体膜组分1乳腺癌裸鼠模型对乳腺肿瘤组织Ki-67表达的影响

Effect of tamoxifen on Ki-67 expression in breast tumor tissue of nude mice transfected with progesterone receptor membrane component 1

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