他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变

doi:10.3969/j.issn.1006-7795.2019.04.009

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (4): 539-543.doi: 10.3969/j.issn.1006-7795.2019.04.009

他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变

王月姣¹, 阮祥燕^1,2, 谷牧青¹, 蔡桂举¹, 李雪¹, 张凌燕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:2018-05-20 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），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），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）。

Tamoxifen treated breast cancer xenograft in nude mice and uterine pathological changes

Wang Yuejiao¹, Ruan Xiangyan^1,2, Gu Muqing¹, Cai Guiju¹, Li Xue¹, Zhang Lingyan¹, 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:2018-05-20 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),The First Batch of Beijing Maternal and Child Health Specialist Demonstration Units "Menopausal Health Specialist"(2018/01-2020/12), Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20181401),Beijing Municipality Health Technology High-level Talent (2014-2-016).

摘要/Abstract

摘要： 目的研究经他莫昔芬治疗后乳腺癌异种移植瘤裸鼠的子宫病理改变，及孕激素治疗是否会影响乳腺癌细胞的增生及他莫昔芬的治疗效果。方法将25只裸鼠皮下植入雌二醇（estradiol，E2）缓释片（0.72 mg/60 d），并建立MCF7乳腺癌细胞荷瘤模型，记录肿瘤体积，荷瘤43 d后，将裸鼠采用数字表法随机分为4个组，每组6只，分别为：安慰剂组、黄体酮组、他莫昔芬组、他莫昔芬联合黄体酮组。56 d后，处死裸鼠取瘤体及子宫，进行HE染色及肿瘤生长曲线绘制。结果裸鼠肿瘤生长速度结果显示：与安慰剂组相比，单用黄体酮未促进乳腺癌的额外增生（P>0.05），他莫昔芬治疗后，乳腺癌组织体积明显缩小（P<0.01）。裸鼠肿瘤HE染色可见：肿瘤组织较疏松，肿瘤细胞数量明显减少，可见坏死的肿瘤细胞及中性粒细胞和淋巴细胞浸润。子宫内膜HE染色结果显示，子宫腺体数目增多，腺细胞核大深染，部分出现异型性，出现子宫内膜不典型增生的病理改变。子宫腺体个数统计结果显示：与安慰剂组相比，经他莫昔芬治疗后的子宫内膜腺体数量增加明显（P<0.01），单用孕激素子宫内膜腺体数量无明显增加（P>0.05）。结论在乳腺癌异种移植瘤裸鼠中，他莫昔芬治疗后肿瘤体积明显缩小，但子宫腺体明显增加，呈不典型增生病理改变；单用孕激素未促进乳腺癌细胞明显增生，子宫内膜无明显增生，孕激素的应用不能拮抗他莫昔芬导致的子宫内膜不典型增生。

关键词: 他莫昔芬, 裸鼠, 乳腺癌移植瘤, 激素治疗, 子宫内膜

Abstract: Objective To investigate the pathological changes of uterus in nude mice with breast cancer xenograft treated with tamoxifen (TAM), and effect of progesterone treatment on the proliferation of breast cancer and therapeutic efficacy of tamoxifen. Methods Prospective, randomized, placebo-controlled four-arm study in xenotransplantations:MCF7 cells were injected into nude mice. Estradiol (E2) pellets were implanted. After 43 days, the breast cancer xenograft was treated with progesterone (P) or TAM or TAM plus P or placebo. All four groups (6 mice/group) were further monitored for 56 days. After 56 days, the mice were sacrificed and take the tumor and uterus. Fresh tissue was immediately stored in 4% paraformaldehyde for hematoxylin and eosin (HE) staining and tumor growth curve mapping.Results Tumor growth curve showed that progesterone group did not promote additional proliferation of breast cancer compared with placebo group (P>0.05). Breast cancer tissue volume decreased significantly after tamoxifen treatment (P<0.01). The HE staining result showed that the tumor tissue was loose connective and the number of tumor cells decreased. Endometrium HE staining showed that the number of glands increased, and glands cells were hyperchromatic, some of which presented atypia and pathological results of endometrial dysplasia. Compared with the placebo group, the number of endometrial glands increased significantly after tamoxifen treatment (P<0.01), while that of the progesterone group did not increase (P>0.05). Conclusion In the nude mice with breast cancer, the tumor volume was significantly reduced after tamoxifen treatment, but the glands were increased, indicating endometrial dysplasia. Progesterone alone did not promote the obvious proliferation of xenotransplantations, without obvious endometrial hyperplasia, Therefore the application of progesterone did not significantly antagonize tamoxifen.

Key words: tamoxifen, nude mice, breast cancer xenograft, hormone therapy, endometrium

中图分类号:

R737.9

王月姣, 阮祥燕, 谷牧青, 蔡桂举, 李雪, 张凌燕, Alfred O. Mueck. 他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变[J]. 首都医科大学学报, 2019, 40(4): 539-543.

Wang Yuejiao, Ruan Xiangyan, Gu Muqing, Cai Guiju, Li Xue, Zhang Lingyan, Alfred O. Mueck. Tamoxifen treated breast cancer xenograft in nude mice and uterine pathological changes[J]. Journal of Capital Medical University, 2019, 40(4): 539-543.

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他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变

Tamoxifen treated breast cancer xenograft in nude mice and uterine pathological changes

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