视黄醇结合蛋白7调控Akt/mTOR信号通路对乳腺癌细胞增殖和迁移侵袭的影响  

Effects of RBP7 on proliferation,migration and invasion of breast cancer cells and regulation of Akt/mTOR signaling pathway

作　　者：秦朝晖[1] 李蔚萍[1] 胡天华[1] 程爱群[1] 洪丽霞 QIN Zhaohui;LI Weiping;HU Tianhua;CHENG Aiqun;HONG Lixia(Department of Breast Surgery,Huadong Hospital Affiliated to Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华东医院乳腺外科,上海200040

出　　处：《临床肿瘤学杂志》2023年第8期673-678,共6页Chinese Clinical Oncology

摘　　要：目的探讨视黄醇结合蛋白7(RBP7)调控蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对乳腺癌细胞增殖和迁移侵袭的影响。方法GEPIA网站用于分析乳腺癌组织的RBP7表达,实时定量PCR(qPCR)用于检测乳腺癌细胞(MCF7、SKBR-3、BT474、T47D、BT549和MDA-MB-231)的RBP7表达。将MDA-MB-231细胞分为pcDNA3.1组(阴性对照)、pcDNA3.1-RBP7组(上调RBP7表达)和pcDNA3.1-RBP7+3BDO组(上调RBP7表达且增强mTOR活性)。qPCR和Western blot用于检测磷酸化Akt(p-Akt)、磷酸化mTOR(p-mTOR)和c-Myc的表达。MTT法、划痕愈合实验和Transwell小室实验检测MDA-MB-231细胞的增殖、迁移和侵袭情况。结果RBP7在乳腺癌组织和细胞中低表达(P<0.05)。生物信息学分析显示RBP7低表达乳腺癌患者的预后较差。pcDNA3.1-RBP7组p-Akt、p-mTOR和c-Myc的表达低于pcDNA3.1组(P<0.05);而pcDNA3.1-RBP7+3BDO组p-Akt、p-mTOR和c-Myc的表达高于pcDNA3.1-RBP7组(P<0.05)。此外,pcDNA3.1-RBP7组MDA-MB-231细胞的增殖、迁移和侵袭能力均弱于pcDNA3.1组(P<0.05),而pcDNA3.1-RBP7+3BDO组MDA-MB-231细胞的增殖、迁移和侵袭能力均强于pcDNA3.1-RBP7组(P<0.05)。结论RBP7通过调控Akt/mTOR通路抑制乳腺癌细胞的增殖、迁移和侵袭,可能为乳腺癌患者提供一种新的治疗干预手段。Objective To clarify the function of retinol binding protein 7(RBP7)on proliferation,migration and invasion of breast cancer cells via regulating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods GEPIA was conducted to analyze RBP7 expression in breast cancer tissues,and qPCR was applied to detect RBP7 expression in multiple breast cancer cell lines(MCF7,SKBR-3,BT474,T47D,BT549 and MDA-MB-231).MDA-MB-231 cells were divided into pcDNA3.1 group(negative control),pcDNA3.1-RBP7 group(overexpression of RBP7)and pcDNA3.1-RBP7+3BDO group(overexpression of RBP7 and mTOR activator).MTT,wound-healing and Transwell chamber assays were applied to measure the proliferation,migration and invasion of MDA-MB-231 cells.Phosphorylated Akt(p-Akt),phosphorylated mTOR(p-mTOR)and c-Myc expression levels were measured by qPCR and Western blot.Results RBP7 were lowly expressed in breast cancer tissues and cells(P<0.05).Bioinformatics analysis showed that breast cancer patients with low RBP7 expression manifested a poorer prognosis.The expressions of p-Akt,p-mTOR and c-Myc were attenuated in pcDNA3.1-RBP7 group as compared with pcDNA3.1 group(P<0.05)and promoted in pcDNA3.1-RBP7+3BDO group as compared with pcDNA3.1-RBP7 group(P<0.05).In addition,the proliferation,migration and invasion abilities of MDA-MB-231 cells were significantly declined in pcDNA3.1-RBP7 group as compared with pcDNA3.1 group(P<0.05),and elevated in pcDNA3.1-RBP7+3BDO group as compared with pcDNA3.1-RBP7 group(P<0.05).Conclusion RBP7 could suppress proliferation,migration and invasion of breast cancer cells through regulating Akt/mTOR pathway,which may offer a new therapeutic intervention for breast cancer patients.

关 键 词：乳腺癌 视黄醇结合蛋白7 蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号 侵袭迁移 

分 类 号：R737.9[医药卫生—肿瘤]