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Prolyl hydroxylase 3 involvement in lung cancer progression under hypoxic conditions: association with hypoxia-inducible factor-1α and pyruvate kinase M2
- Source :
- Journal of Thoracic Disease. 11:3941-3950
- Publication Year :
- 2019
- Publisher :
- AME Publishing Company, 2019.
-
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
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
medicine.diagnostic_test
business.industry
Angiogenesis
PKM2
medicine.disease
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Hypoxia-inducible factors
Western blot
Apoptosis
medicine
Cancer research
Original Article
Viability assay
business
Lung cancer
030217 neurology & neurosurgery
Pyruvate kinase
Subjects
Details
- ISSN :
- 20776624 and 20721439
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Disease
- Accession number :
- edsair.doi.dedup.....eb8a8107ccdd356a96b2fcf0264441a1