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    梁馨予, 刘佳君, 刘建文. 敲低EEF1A2增强拉帕替尼对HER2+乳腺癌细胞的药效[J]. 华东理工大学学报(自然科学版), 2022, 48(1): 59-69. DOI: 10.14135/j.cnki.1006-3080.20210114001
    引用本文: 梁馨予, 刘佳君, 刘建文. 敲低EEF1A2增强拉帕替尼对HER2+乳腺癌细胞的药效[J]. 华东理工大学学报(自然科学版), 2022, 48(1): 59-69. DOI: 10.14135/j.cnki.1006-3080.20210114001
    LIANG Xinyu, LIU Jiajun, LIU Jianwen. Knockdown of EEF1A2 Enhanced the Efficacy of Lapatinib on HER2+ Breast Cancer Cells[J]. Journal of East China University of Science and Technology, 2022, 48(1): 59-69. DOI: 10.14135/j.cnki.1006-3080.20210114001
    Citation: LIANG Xinyu, LIU Jiajun, LIU Jianwen. Knockdown of EEF1A2 Enhanced the Efficacy of Lapatinib on HER2+ Breast Cancer Cells[J]. Journal of East China University of Science and Technology, 2022, 48(1): 59-69. DOI: 10.14135/j.cnki.1006-3080.20210114001

    敲低EEF1A2增强拉帕替尼对HER2+乳腺癌细胞的药效

    Knockdown of EEF1A2 Enhanced the Efficacy of Lapatinib on HER2+ Breast Cancer Cells

    • 摘要: 探究乳腺癌中翻译延伸因子1α2(EEF1A2)与HER2之间的潜在关系。通过TCGA(The Cancer Genome Atlas)分析EEF1A2 mRNA在乳腺癌中的表达情况;利用MTT(噻唑蓝)、克隆形成和Transwell实验方法检测了HER2+乳腺癌细胞SKBR3和MDA-MB-453在EEF1A2蛋白表达敲低及拉帕替尼处理后的增殖、迁移和凋亡情况。结果表明EEF1A2 mRNA在HER2+乳腺癌组织中高表达,并降低了HER2+乳腺癌患者的总生存率;同时,SKBR3和MDA-MB-453细胞中EEF1A2敲低会增强拉帕替尼对细胞体外增殖、迁移和侵袭的抑制,以及对凋亡的促进。Western blot实验结果表明,下调EEF1A2会增强拉帕替尼对HER2+乳腺癌细胞中HER2/AKT通路的抑制。EEF1A2蛋白可成为改善拉帕替尼治疗HER2+乳腺癌效果的潜在靶标。

       

      Abstract: Breast cancer (BRCA) is the most frequently diagnosed cancer in females over the world. HER2-positive (HER2+) breast cancer accounts for 15%~20% of total breast cancer, which related to HER2 overexpression and rapid deteriorations of cancer. Lapatinib is a dual EGFR/HER2 inhibitor for HER2+ breast cancer therapy, while the drug resistance is the main reason for treatment failure. As a critical component of the translational machinery, eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was significantly upregulated to promote the cancer progression in various tumors like breast tumor. This study explored the potential relation of EEF1A2 and HER2 in breast cancer. The EEF1A2 mRNA expressions in human breast cancer tissues were analyzed by TCGA online data. The differences of EEF1A2 mRNA levels and its impacts to prognosis between HER2-positive breast cancer tissues and HER2-negative ones were further detected. The EEF1A2-knockdown plasmid was constructed via shRNA for the further transfection. Subsequently, we explored the proliferation, metastasis and apoptosis of SKBR3 and MDA-MB-453, the HER2-positive breast cancer cells, treated with EEF1A2-knockdown and lapatinib via MTT, colony formation, transwell assay and apoptosis assay, respectively. Results of TCGA analysis showed that EEF1A2 mRNA overexpressed in breast cancer tissues. Most importantly, the level of EEF1A2 mRNA in HER2-positive breast cancer tissues was significantly higher than that in HER2-negative subtype. The higher level of EEF1A2 mRNA correlated with the lower overall survival in HER2-positive breast cancer. While the EEF1A2-knockdown enhanced the lapatinib’s impacts on proliferation, migration, invasion and apoptosis of SKBR3 and MDA-MB-453 in vitro. Western blot showed the EEF1A2-knockdown augmented the inhibition on HER2/AKT pathway induced by lapatinib in cells. Thus, we suggested that EEF1A2 could be a potential target to improve the therapy of HER2-positive breast cancer treated with lapatinib.

       

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