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FNC inhibits non-small cell lung cancer by activating the mitochondrial apoptosis pathway

Genes & Genomics 2022년 44권 1호 p.123 ~ 131
Jing Xiang, Niu Shuai, Liang Yi, Chen Huiping, Wang Ning, Peng Youmei, Ma Fang, Yue Wanying, Zhang Yi, Zhang Yan,
소속 상세정보
 ( Jing Xiang ) - Zhengzhou University School of Pharmaceutical Science
 ( Niu Shuai ) - Zhengzhou University School of Pharmaceutical Science
 ( Liang Yi ) - Zhengzhou University School of Pharmaceutical Science
 ( Chen Huiping ) - Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences
 ( Wang Ning ) - Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences
 ( Peng Youmei ) - Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences
 ( Ma Fang ) - Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences
 ( Yue Wanying ) - Zhengzhou University School of Pharmaceutical Science
 ( Zhang Yi ) - Zhengzhou University First Affiliated Hospital Department of Orthopaedic Surgery
 ( Zhang Yan ) - Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences

Abstract


Background: Previously, we published that 4′-azid-2′-deoxy-2′-fluorarabinoside (FNC), a novel cytosine nucleoside analog, has good anti-viral and anti-tumor activity.

Objective: This study aimed to further explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC).

Methods: 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).

Results: 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.

Conclusion: 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.

키워드

FNC; NSCLC; Apoptosis; Metastasis; Xenograft

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