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

Biomedicine & Pharmacotherapy

Jeng-Yuan Wu¹  Hsin-Ell Wang²  Ming-Hsin Li³  Yu-Chang Liu⁴  Mao-Chi Weng⁵  Fei-Ting Hsu⁶  Jing Gung Chung⁷ 

[1] Department of Biotechnology, Asia University, Taichung, Taiwan;Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan;Isotope Application Division, Institute of Nuclear Energy Research, Atomic Energy Council, Taiwan;Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan;Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan;Isotope Application Division, Institute of Nuclear Energy Research, Atomic Energy Council, Taiwan;

关键词: Non-small cell lung cancer;    Regorafenib;    AKT;    NF-κB;    Apoptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown