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

Content Provider	Semantic Scholar
Author	Qian, Jialin Bai, Hao Gao, Zhiqiang Dong, Yu ‐ Ze Pei, Jiancheng Ma, Meili Han, Baohui
Copyright Year	2016
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.
Starting Page	1738
Ending Page	1744
Page Count	7
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://ftp.ncbi.nlm.nih.gov/pub/pmc/6c/1e/ol-11-03-1738.PMC4774571.pdf
Alternate Webpage(s)	https://www.spandidos-publications.com/ol/11/3/1738/download
PubMed reference number	4774571
Volume Number	11
Journal	Oncology letters
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase Annexins Apoptosis Carcinogenesis Cell Count Cell Proliferation Cisplatin Endothelial Growth Factors Hyperplasia Iodides Leukemia, B-Cell Mast/Stem Cell Growth Factor Receptor Kit, human Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Mitogens Neoplasms Non-Small Cell Lung Carcinoma Phosphatidylinositols Pigment Epithelium Promotion (action) Propidium Iodide Proto-Oncogene Proteins c-akt RNA, Small Interfering SERPINF1 gene Small cell carcinoma of lung Staining method Western Blot caspase conversion of ds siRNA to ss siRNA involved in chromatin silencing by small RNA
Content Type	Text
Resource Type	Article