STAT1 modification improves therapeutic effects of interferons on lung cancer cells

Journal of Translational Medicine
Junjie ChenChengshui Chen

Abstract

Interferons (IFNs) have potent anti-proliferative, pro-apoptotic, and immunomodulatory activities against cancer. However, the clinical utility of IFNs is limited by toxicity and pharmacokinetics making it difficult to achieve sustained therapeutic levels especially in solid tumors. Signal Transducer and Activator of Transcription 1 (STAT1) or a modified STAT1 (designated STAT1-CC) that is hyper-responsive to IFN were overexpressed in lung cancer SPC-A-1 and H1299 cells using lentiviral vectors. Transduction efficiency was monitored using enhanced green fluorescent protein (EGFP) expression. After transduction, cells were treated with interferon-gamma (IFN-γ) or interferon-beta (IFN-β) and monitored for cell proliferation, migration, and invasiveness using Cell Counting Kit-8 and transwell chamber assays and for apoptosis using Annexin V detection by flow cytometry. In addition, levels of STAT1, STAT1 Tyr-701 phosphorylation (pSTAT1), fibronectin, and β-catenin were determined using western blotting. In the case of IFN-γ stimulation, levels of S100A4, proliferating cell nuclear antigen (PCNA), and c-fos expression were also determined. We found that expression of STAT1 or STAT1-CC enhanced the effect of IFN-γ and, IFN-β on inhi...Continue Reading

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Citations

Apr 10, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Long JinChul Woo Yang
Jan 10, 2017·Food & Function·Carla NunesJoão Laranjinha
Jan 11, 2018·Transplantation·Long JinChul Woo Yang
Apr 9, 2019·Cell Biology International·Dongmei GaoJicheng Li
Sep 15, 2017·Environmental Science and Pollution Research International·Yan CuiQingbi Zhang
Oct 19, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Aveen N AdhamThomas Efferth
Mar 18, 2021·The Journal of Pharmacy and Pharmacology·Yaprak Dilber Şimay DemirMustafa Ark

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Methods Mentioned

BETA
PCR
Protein Assay
Electrophoresis
flow cytometry
transfection
ubiquitination
acetylation

Software Mentioned

Image Lab

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