| 摘要: |
| ［摘要］ 目的 探究人乳腺癌裸鼠移植动物模型体内孕激素受体膜组分1（PGRMC1）在黄体酮与炔诺酮（NET）刺激下对乳腺癌异种移植瘤增殖影响的差异性。方法 构建PGRMC1稳定表达的人乳腺癌细胞系（MCF7），36只雌性BALB/c-nu裸鼠按随机数字表法分为MCF7/HA-PGRMC1组（n=18）和MCF7/HA-Vector组（n=18）。各鼠于颈部皮下包埋雌二醇（E2）缓释片。24 h后两组裸鼠左、右侧面皮下分别注射MCF7/HA-PGRMC1和MCF7/HA-Vector细胞悬液150 μL，注射细胞数为1×107个。肿瘤生长至100 mm3左右，将两组裸鼠进行组内分组，分别皮下联合包埋安慰剂、黄体酮缓释片、NET缓释片，即E2+安慰剂亚组（n=6）、E2+黄体酮亚组（n=6）、E2+NET亚组（n=6）。记录肿瘤体积变化，绘制肿瘤生长曲线。45 d后完整摘除肿瘤组织免疫组化染色检测PGRMC1和Ki67表达情况。结果 MCF7/HA-PGRMC1株系构建成功，在MCF7/HA-PGRMC1组中，与E2+安慰剂亚组相比，E2+黄体酮亚组肿瘤增长差异无统计学意义（P>0.05），而E2+NET亚组肿瘤明显生长（P<0.05）。在MCF7/HA-Vector组中，与E2+安慰剂亚组相比，E2+NET亚组、E2+黄体酮亚组的肿瘤增长差异均无统计学意义（P>0.05）。在MCF7/HA-PGRMC1组中，E2+NET亚组Ki67呈强阳性表达，PGRMC1与Ki67表达呈正相关（r=0.892，P=0.014）。结论 该实验在裸鼠体内证实PGRMC1过表达可特异性介导NET联合E2的促乳腺癌增殖效应，而联合黄体酮并没有促进额外增殖。这一发现为临床激素治疗中孕激素类型的选择提供了关键的动物实验依据。 |
| 关键词: 孕激素受体膜组分1 乳腺癌 黄体酮 炔诺酮 裸鼠乳腺癌模型 激素治疗 |
| DOI：10.3969/j.issn.1674-3806.2025.11.03 |
| 分类号: |
| 基金项目:首都医科大学附属北京妇产医院/北京妇幼保健院“芒种计划”科技创新能力提升专项项目（编号：FCYYMZB202505）；首都医科大学附属北京妇产医院/北京妇幼保健院“优青人才”计划专项项目（编号：YQRC201807）；北京市医院管理局青年人才培养“青苗”计划专项项目（编号：QML20181401） |
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| Differential effects of PGRMC1-mediated different progesterones on proliferation of breast cancer |
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ZHAO Yue1, JU Rui2, XIE Dan1, ZHANG Zheng1, ZHU Jianguo1, ZHANG E1, LI Li3
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1.Medical Administration Division, Beijing Obstetrics and Gynecology Hospital, Capital Medical University/Beijing Maternal and Child Health Care Hospital, Beijing 100026, China; 2.Drug Clinical Trial Institution Office, Beijing Obstetrics and Gynecology Hospital, Capital Medical University/Beijing Maternal and Child Health Care Hospital, Beijing 100026, China; 3.Hospital Administration Office, Beijing Obstetrics and Gynecology Hospital, Capital Medical University/Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
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| Abstract: |
| ［Abstract］ Objective To explore the differences in effects of progesterone receptor membrane component 1(PGRMC1) in a nude mouse model with human breast cancer xenografts on the proliferation of breast cancer xenografts under the stimulation of progesterone and norethisterone(NET). Methods A human breast cancer cell line(MCF7) with stable expression of PGRMC1 was constructed. Thirty-six female BALB/c-nu nude mice were divided into MCF7/HA-PGRMC1 group(n=18) and MCF7/HA-Vector group(n=18) according to random number table method. Estradiol(E2) sustained-release tablets were subcutaneously embedded in the neck of each mouse. After subcutaneous embedding of E2 sustained-release tablets for 24 hours, MCF7/HA-PGRMC1 and MCF7/HA-Vector cell suspensions were respectively injected into the subcutaneous tissues on the left and right sides of the nude mice in the two groups at a dose of 150 μL, with a cell count of 1×107. When tumors grew to about 100 mm3 in size, the nude mice in the two groups were further divided into three subgroups: the E2+placebo subgroup(receiving subcutaneous embedding of E2 plus placebo)(n=6), the E2+progesterone subgroup(receiving subcutaneous embedding of E2 plus progesterone sustained-release tablets)(n=6) and the E2+NET subgroup(receiving subcutaneous embedding of E2 plus NET sustained-release tablets)(n=6). The volume changes of the tumors were recorded and tumor growth curves were plotted. After 45 days, the tumor tissues were completely excised, and immunohistochemical staining was performed to detect PGRMC1 and Ki67 expressions in the xenograft tissues. Results The MCF7/HA-PGRMC1 strain was successfully constructed. In the MCF7/HA-PGRMC1 group, there was no statistically significant difference in tumor growth between the E2+progesterone subgroup and the E2+placebo subgroup(P>0.05), while the E2+NET subgroup showed significant tumor growth compared with the E2+placebo subgroup(P<0.05). In the MCF7/HA-Vector group, there was no statistically significant difference in tumor growth between the E2+NET subgroup and the E2+placebo subgroup(P>0.05) as well as between the E2+progesterone subgroup and the E2+placebo subgroup(P>0.05). In the MCF7/HA-PGRMC1 group, Ki67 showed strong positive expression in the E2+NET subgroup, and PGRMC1 was positively correlated with Ki67 expression(r=0.892, P=0.014). Conclusion This experiment confirms that overexpression of PGRMC1 can specifically mediate the proliferation-promoting effect of NET combined with E2 on breast cancer in nude mice in vivo, while the combination with progesterone does not promote the additional proliferation. This discovery provides crucial animal experimental evidence for the selection of progesterone types in clinical hormone therapy. |
| Key words: Progesterone receptor membrane component 1(PGRMC1) Breast cancer Progesterone Norethisterone(NET) A nude mouse model with breast cancer Hormone therapy |
