摘要
为了考察血管内皮生长因子(VEGF)和癌胚抗原(CEA)在乳腺癌中的表达及与血管生成的关系,本研究应用RT-PCR和Western blotting检测了30份乳腺癌组织和癌旁组织中的VEGF和CEA表达,并比较了人乳腺癌腺癌细胞系(MCF-7)和人正常乳腺上皮细胞(MCF10A)中的VEGF和CEA的表达。通过转染含有VEGF sh RNA(sh-VEGF)和CEA shRNA(sh-CEA)的慢病毒来敲低基因表达。将MCF-7和HUVEC的细胞共培养来模拟肿瘤微环境,并通过小管形成测定和细胞侵袭试验来评价VEGF和CEA对血管生成的影响。研究显示,与癌旁组织相比,VEGF和CEA在乳腺癌组织中明显上调(p<0.05)。与MCF10A相比,MCF-7细胞中的VEGF和CEA的水平明显升高(p<0.05)。VEGF和CEA的异常表达与TNM分期和淋巴结转移相关(p<0.05)。敲低VEGF和CEA均可显著抑制MCF-7细胞中Notch1、Dell4和Jagged1的表达(p<0.05)。敲低VEGF和CEA均抑制了HUVEC细胞的小管形成能力和侵袭能力(p<0.05)。总之,VEGF和CEA在乳腺癌中明显上调,并且与患者的不良预后相关。敲低VEGF和CEA可通过抑制Notch1信号的激活来抑制乳腺癌细胞的侵袭和血管生成。
To investigate the expression of vascular endothelial growth factor(VEGF)and carcinoembryonic antigen(CEA)in breast cancer and their relationship with angiogenesis.In this study,RT-PCR and Western blotting were used to detect the expression of VEGF and CEA in 30 breast cancer tissues and adjacent tissues.The expressions of VEGF and CEA in human breast cancer adenocarcinoma cell line(MCF-7)and human normal breast epithelial cells(MCF10 A)were compared.Gene expression was knocked down by transfection of a lentivirus containing VEGF shRNA(sh-VEGF)and CEA shRNA(sh-CEA).MCF-7 and HUVEC cells were co-cultured to mimic the tumor microenvironment,and the effects of VEGF and CEA on angiogenesis were evaluated by tubule formation assays and cell invasion tests.Studies showed that VEGF and CEA were significantly upregulated in breast cancer tissues compared to adjacent tissues(p<0.05).Compared with MCF10 A,the levels of VEGF and CEA in MCF-7 cells were significantly increased(p<0.05).The abnormal expression of VEGF and CEA was related to TNM stage and lymph node metastasis(p<0.05).Knockdown of VEGF and CEA significantly inhibited the expression of Notch1,Dell4 and Jagged1 in MCF-7 cells(p<0.05).Knockdown of VEGF and CEA both inhibited the ability of tubule formation and invasion of HUVEC cells(p<0.05).In conclusion,VEGF and CEA are significantly up-regulated in breast cancer and are associated with poor patient prognosis.Knockdown of VEGF and CEA can inhibit the invasion and angiogenesis of breast cancer cells by inhibiting the activation of Notch1 signaling.
作者
王秀梅
Wang Xiumei(Yuncheng Vocational Nursing College,Yuncheng,044000)
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2020年第5期2311-2317,共7页
Genomics and Applied Biology
关键词
乳腺癌
血管内皮生长因子
癌胚抗原
血管生成
Notch1信号
肿瘤转移
Breast cancer
Vascular endothelial growth factor(VEGF)
Carcinoembryonic antigen(CEA)
Angiogenesis
Notch1 signal
Tumor metastasis
