Xiao Chu1, Ming Xiang1, Liang Feng1, Hui Liu1, Chao Zhou2. 1. Department of Thoracic Surgery, Fifth People's Hospital of Shanghai Fudan University, Shanghai 200240, China. 2. Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China.
Abstract
BACKGROUND: Previous studies have suggested that the functions of prolyl hydroxylase 3 (PHD3) in tumor growth, apoptosis and angiogenesis are essentially dependent on hypoxia-inducible factor (HIF)-1α signaling. Nevertheless, whether PHD3 represents a promising tumor suppressor target remains to be clarified. To provide insight into the therapeutic potential of PHD3 in lung cancer, this study examined the effects of PHD3 expression on HIF-1α and pyruvate kinase M2 (PKM2), as well as on lung cancer cell proliferation, migration, and invasion. METHODS: The model of hypoxia was established in A549 and SK-MES-1 cells with 200 µM CoCl2 treatment, and verified by western blot and immunocytochemical staining. The expression levels of PKM2 and HIF-1α were determined by western blot after overexpression or depletion of PHD3 in A549 and SK-MES-1 cells. In addition, cell viability, migration and invasion were measured, respectively. RESULTS: Establishment of hypoxia in A549 and SK-MES-1 cells resulted in significant decreases in PHD3 expression and remarkable increase in PKM2 expression in 24 hrs. Overexpression of PHD3 in A549 and SK-MES-1 cells decreased HIF-1α and PKM2 expression. In contrast, PHD3 knockdown increased HIF-1α and PKM2 (P<0.05). In addition, the viability, migration and invasion of A549 and SK-MES-1 cells were significantly decreased with PHD3 overexpression, but dramatically increased with PHD3 depletion (P<0.05). CONCLUSIONS: PHD3 is involved in lung cancer progression, and might be a promising therapeutic target for cancers. 2019 Journal of Thoracic Disease. All rights reserved.
BACKGROUND: Previous studies have suggested that the functions of prolyl hydroxylase 3 (PHD3) in tumor growth, apoptosis and angiogenesis are essentially dependent on hypoxia-inducible factor (HIF)-1α signaling. Nevertheless, whether PHD3 represents a promising tumor suppressor target remains to be clarified. To provide insight into the therapeutic potential of PHD3 in lung cancer, this study examined the effects of PHD3 expression on HIF-1α and pyruvate kinase M2 (PKM2), as well as on lung cancer cell proliferation, migration, and invasion. METHODS: The model of hypoxia was established in A549 and SK-MES-1 cells with 200 µM CoCl2 treatment, and verified by western blot and immunocytochemical staining. The expression levels of PKM2 and HIF-1α were determined by western blot after overexpression or depletion of PHD3 in A549 and SK-MES-1 cells. In addition, cell viability, migration and invasion were measured, respectively. RESULTS: Establishment of hypoxia in A549 and SK-MES-1 cells resulted in significant decreases in PHD3 expression and remarkable increase in PKM2 expression in 24 hrs. Overexpression of PHD3 in A549 and SK-MES-1 cells decreased HIF-1α and PKM2 expression. In contrast, PHD3 knockdown increased HIF-1α and PKM2 (P<0.05). In addition, the viability, migration and invasion of A549 and SK-MES-1 cells were significantly decreased with PHD3 overexpression, but dramatically increased with PHD3 depletion (P<0.05). CONCLUSIONS: PHD3 is involved in lung cancer progression, and might be a promising therapeutic target for cancers. 2019 Journal of Thoracic Disease. All rights reserved.
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