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Downregulation of HIF-1α inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells.

Abstract：

:Lung cancer, specifically non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality in the world. In previous years, almost no significant advancements have been made towards the molecular characterization of NSCLC, which highlights the requirement for novel target genes. Hypoxia inducible factor-1α (HIF-1α) is known to be essential in tumorigenesis, as it regulates the expression of numerous factors that are involved in angiogenesis, cellular proliferation and apoptosis. However, no direct association between HIF-1α and NSCLC treatment has previously been established. The aim of the present study was to characterize the effect of HIF-1α on NSCLC and to explore the possible mechanism. Additionally, HIF-1α small interfering (si)RNA and diamminedichloroplatinum (DDP) were used in combination to explore the combined effects on NSCLC cells. Lung carcinoma NCI-H157 cells were treated with HIF-1α small interfering (si)RNA, 5 µg/ml DDP or a combination of the two, and the proliferation, apoptosis and invasion ability of the cells were detected using a cell counting kit-8 assay, Annexin V/propidium iodide staining and a Transwell assay, respectively. In addition, the protein levels of caspase-3/9, anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)PI3K, protein kinase B (AKT), p-AKT, extracellular signal-regulated kinase (ERK) and p-ERK were detected using western blot analysis. Similar to DPP treatment, HIF-1α siRNA treatment may reduce cell proliferation and the invasiveness of tumor cells while promoting apoptosis. Additionally, HIF-1α siRNA may increase the levels of the apoptotic proteins caspases 3 and 9 and inhibit the expression of Bcl-2. These anti-tumor effects may be acting through the VEGF/PEDF, PI3K/AKT and Raf/mitogen-activated protein kinase kinase/ERK signaling pathways. The effects of HIF-1α siRNA may be strengthened by DDP. The present data indicated that HIF-1α siRNA is important in the inhibition of NSCLC cells. Additionally, the effects of HIF-1α siRNA may be strengthened by DDP, which suggests that HIF-1α siRNA may be combined with DDP for the treatment of tumors.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Qian J,Bai H,Gao Z,Dong YU,Pei J,Ma M,Han B

doi

10.3892/ol.2016.4150

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

1738-1744

issue

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-4150

journal_volume

pub_type

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Downregulation of HIF-1α inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells.