Zhao Jinjin, Zhang Haiguang, Liu Yaqian, Lu Guangjian, Wang Zhaohui, Mo Qingjiang, Wang Guoqiang, Shen Yanfei, Jiao Luyang
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
Heliyon. 2024 Sep 14;10(19):e37900. doi: 10.1016/j.heliyon.2024.e37900. eCollection 2024 Oct 15.
Lung metastasis, a leading cause of breast cancer mortality, lacks effective therapeutic options. Hypoxia-inducible factor 1-alpha (HIF-1α) plays important roles in breast cancer progression, but its direct impact on lung metastasis remains unclear. Herein, in this study, we investigated the role of HIF-1α in breast cancer lung metastasis and the potential of targeting it for therapeutic benefit. HIF-1α expression was knocked down in the 4T1 mouse mammary carcinoma cell line using a lentiviral vector. HIF-1α knockdown significantly reduced the migratory ability of 4T1 cells in vitro and lung metastasis in a mouse model. Mechanistically, HIF-1α knockdown decreased the expression of matrix metalloproteinases (MMP-2 and MMP-9) that degrade the extracellular matrix and suppressed the epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin and decreasing vimentin expression. The findings of this study demonstrate that HIF-1α knockdown effectively inhibits lung metastasis of 4T1 cells both in vitro and in vivo by suppressing EMT. These results underscore a promising new approach for managing breast cancer metastasis.
肺转移是乳腺癌死亡的主要原因，目前缺乏有效的治疗方法。缺氧诱导因子1α（HIF-1α）在乳腺癌进展中起重要作用，但其对肺转移的直接影响尚不清楚。在此，在本研究中，我们研究了HIF-1α在乳腺癌肺转移中的作用以及靶向它以获得治疗益处的潜力。使用慢病毒载体在4T1小鼠乳腺癌细胞系中敲低HIF-1α表达。敲低HIF-1α显著降低了4T1细胞在体外的迁移能力以及在小鼠模型中的肺转移。机制上，敲低HIF-1α降低了降解细胞外基质的基质金属蛋白酶（MMP-2和MMP-9）的表达，并通过增加E-钙黏蛋白和降低波形蛋白表达来抑制上皮-间质转化（EMT）。本研究结果表明，敲低HIF-1α通过抑制EMT在体外和体内均有效抑制4T1细胞的肺转移。这些结果强调了一种有前景的治疗乳腺癌转移的新方法。
