不同雌激素浓度对重组人骨形态发生蛋白2干预乳腺癌MCF-7细胞生长和迁移影响的体外研究  

In vitro study on the effects of different concentrations of estrogen on the growth and migration of breast cancer MCF-7 cells intervened by recombinant human bone morphogenetic protein-2

作　　者：刘书中[1] 姚思远 吴昀效 刘勇[1] LIU Shu-zhong;YAO Si-yuan;WU Yunxiao(Department of Orthopaedics,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China;School of Public Health,Peking University Health Science Center,Beijing100191,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院骨科,北京100730 [2]北京大学公共卫生学院,北京100191

出　　处：《中国实验诊断学》2023年第6期705-715,共11页Chinese Journal of Laboratory Diagnosis

基　　金：北京协和医学院博士生创新基金项目(2018-1002-02-08);2022年第一批“协和青年学者”支持计划;2021年“骨质疏松和骨矿盐中青年医生优才培养计划暨白求恩·石药骨质疏松科研基金项目”(GX2021D01)。

摘　　要：目的探究不同雌激素浓度对rhBMP-2干预下乳腺癌MCF-7细胞增殖、迁移、侵袭和细胞周期的影响。方法本实验根据处理MCF-7细胞的rhBMP-2、noggin(BMP-2拮抗剂)以及不同雌激素浓度将细胞进行分组。采用MTT试验检测不同作用条件下MCF-7细胞的增殖能力,Transwell迁移试验及侵袭试验评估不同作用条件下细胞迁移及侵袭能力,利用流式细胞仪检测细胞周期并应用qRT-PCR技术对细胞周期蛋白水平进行定量分析。结果较低浓度的雌激素对rhBMP-2干预后的MCF-7细胞增殖有抑制作用,而高浓度的雌激素对rhBMP-2干预后的MCF-7细胞增殖有促进作用。不同浓度的雌激素均可促进rhBMP-2干预后MCF-7细胞的迁移,其中部分浓度具有统计学意义。不同浓度的雌激素对于rhBMP-2干预后MCF-7细胞的侵袭能力有抑制趋势,但均无统计学差异。RhBMP-2和noggin可不同程度影响G1期,不同雌激素浓度对细胞周期并无显著性影响。不同浓度雌激素处理下基因CDK2、CDK4、cyclinD1、cyclinE、p21转录水平有所差异。结论低浓度的雌激素可协同rhBMP-2对乳腺癌MCF-7细胞增殖产生抑制作用,而高浓度雌激素则拮抗了rhBMP-2对MCF-7细胞增殖的抑制作用。在rhBMP-2作用的基础上,雌激素可进一步降低MCF-7细胞的迁移能力,但对侵袭能力作用无明显统计学差异。不同雌激素浓度对细胞周期并没有显著影响,但可能影响多种细胞周期蛋白的表达。Objective To explore the effects of different concentrations of estrogen on the proliferation,migration,invasion and cell cycle of breast cancer MCF-7cells under the intervention of rhBMP-2.Methods In this study,MCF-7 cells were divided into groups according to the different concentrations of rhBMP-2,noggin(BMP-2antagonist)and estrogen.MTT assay was used to detect the proliferation ability of MCF-7cells under different conditions.Transwell migration test and invasion test were used to evaluate the migration and invasion ability of MCF-7cells under different conditions,flow cytometry was used to detect the cell cycle,and qRT-PCR was used to quantitatively analyze the expression level of cyclins.Results Low concentration of estrogen can inhibit the proliferation of MCF-7cells after rh-BMP-2intervention,while high concentration of estrogen can promote the proliferation of MCF-7cells after rhBMP-2 intervention.Different concentrations of estrogen can promote the migration of MCF-7cells after rhBMP-2intervention,some of which have statistical significance.Different concentrations of estrogen inhibited the invasion of MCF-7 cells after rhBMP-2induced,but there was no significant difference.RhBMP-2and noggin could affect G1phase in varying degrees,but different concentrations of estrogen had no significant effect on cell cycle.The transcription levels of CDK2,CDK4,cyclin D1,cyclin E and p21were regulated by different concentrations of estrogen.Conclusion Low concentration of estrogen can cooperate with rhBMP-2to inhibit the proliferation of breast cancer MCF-7cells,while high concentration of estrogen can antagonize the inhibitory effect of rhBMP-2on the proliferation of MCF-7cells.On the basis of rhBMP-2,estrogen can further reduce the migration ability of MCF-7cells,but there is no significant difference in the invasion ability.Different concentrations of estrogen have no significant effect on cell cycle,but may affect the expression of various cyclins.

关 键 词：雌激素浓度 重组人骨形态发生蛋白2 乳腺癌 细胞增殖 迁移和侵袭 

分 类 号：R737.9[医药卫生—肿瘤]