FNC inhibits non-small cell lung cancer by activating the mitochondrial apoptosis pathway
| Autor: | Shuai Niu, Yi Liang, Wanying Yue, Yi Zhang, Junbiao Chang, Qingduan Wang, Huiping Chen, Ning Wang, Youmei Peng, Yan Zhang, Fang Ma, Xiang Jing |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Lung Neoplasms Cell Autophagy-Related Proteins Mice Nude Apoptosis Cytosine Nucleotides Biology Biochemistry Cytosine nucleoside Flow cytometry Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor Genetics medicine Animals Humans Viability assay Cell adhesion Molecular Biology Cell Proliferation Mice Inbred BALB C medicine.diagnostic_test Cell migration Neoplasms Experimental Cadherins Xenograft Model Antitumor Assays Mitochondria respiratory tract diseases Mice Inbred C57BL medicine.anatomical_structure Matrix Metalloproteinase 9 Cell culture Cancer research Matrix Metalloproteinase 2 Signal Transduction |
| Zdroj: | Genes & Genomics. 44:123-131 |
| ISSN: | 2092-9293 1976-9571 |
| DOI: | 10.1007/s13258-021-01179-9 |
| Popis: | Previously, we published that 4′-azid-2′-deoxy-2′-fluorarabinoside (FNC), a novel cytosine nucleoside analog, has good anti-viral and anti-tumor activity. This study aimed to further explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC). FNC was tested in the NSCLC H460 cell line, the Lewis mouse model, and the H460 cell xenograft model. The effects of FNC were assessed by cell viability, transwell migration, and wound scratch analyses of cell migration and invasion. Apoptosis was assessed by flow cytometry. Proteins expression was assessed by western blot and immunohistochemistry staining (IHC). FNC inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner. FNC treatment showed efficacy and low toxicity in the Lewis mouse lung cancer model as well as in the H460 cell xenograft model. Further, FNC induced H460 cell apoptosis through the activation of the mitochondrial pathway. Notably, FNC inhibited invasion by increasing E-cadherin protein and reducing the protein expression of VEGF, MMP-2, MMP-9, and CD31. FNC inhibits NSCLC by activating the mitochondrial apoptosis pathway and regulating the expressions of multiple proteins related to cell adhesion and invasion, highlighting its potential as an NSCLC therapeutic. |
| Databáze: | OpenAIRE |
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