Apoptosis induction and AKT/NF-κB inactivation are associated with regroafenib-inhibited tumor progression in non-small cell lung cancer in vitro and in vivo
| Autor: | Hsin Ell Wang, Fei-Ting Hsu, Mao Chi Weng, Yu Chang Liu, Ming Hsin Li, Jeng Yuan Wu, Jing Gung Chung |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Pyridines Apoptosis NF-κB chemistry.chemical_compound 0302 clinical medicine Non-small cell lung cancer Cell Movement Carcinoma Non-Small-Cell Lung Medicine LY294002 Regorafenib Mice Inbred BALB C NF-kappa B Receptors Death Domain General Medicine 030220 oncology & carcinogenesis Disease Progression Signal Transduction Cell Survival Mice Nude RM1-950 03 medical and health sciences In vivo Cell Line Tumor Animals Humans Neoplasm Invasiveness Viability assay Lung cancer Protein kinase B Cell Proliferation Pharmacology business.industry AKT Phenylurea Compounds medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology chemistry Tumor progression Cancer research Therapeutics. Pharmacology business Proto-Oncogene Proteins c-akt DNA Damage |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 116, Iss, Pp 109032-(2019) |
| ISSN: | 0753-3322 |
| Popis: | Non-small cell lung cancer (NSCLC) is a malignant lung cancer type with poor prognosis. NF-κB, the oncogenic transcription factor, has been recognized as an important mediator in progression of NSCLC. Regorafenib, a multikinase inhibitor, was demonstrated to inhibit tumor progression through suppression of ERK/NF-κB signaling in hepatocellular carcinoma cells in vitro and in vivo. However, whether regorafenib inhibit progression of NSCLC is ambiguous. Thus, the major purpose of present study was to evaluate anticancer efficacy and underlying mechanism of regorafenib on tumor progression in NSCLC in vitro and in vivo. CL-1-5-F4 cells were treated with regorafenib, NF-κB (QNZ) or AKT (LY294002) inhibitor for 24 or 48 h. Then, we performed cell viability assay, NF-κB reporter gene assay, transwell invasion assay and apoptosis related flow cytometry assay on cellular level to verify anti-cancer effect and mechanism of regorafenib. CL-1-5-F4 bearing animal model was treated with vehicle or regorafenib for 28 days. The therapeutic efficacy and mechanism of regorafenib in CL-1-5-F4 bearing animal model were investigated by tumor size evaluation, whole body computer tomography (CT) scan, Haemotoxylin and Eosin (H&E) stain and immunohistochemistry (IHC) stain. Our results demonstrated regorafenib significantly inhibited tumor growth and induced apoptosis through extrinsic/intrinsic pathways in NSCLC in vitro and in vivo. Furthermore, we also found the suppression of AKT/NF-κB signaling was required for regorafenib inhibited expression of progression-related and invasion-related proteins. Our finding indicated apoptosis induction and suppression of AKT/NF-κB signaling were associated with regorafenib-inhibited progression of NSCLC in vitro and in vivo. |
| Databáze: | OpenAIRE |
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