title: Downregulation of leptin inhibits growth and induces apoptosis of lung cancer cells via the Notch and JAK/STAT3 signaling pathways.
abstract: Previous studies have documented that leptin is involved in the pathogenesis of many human cancer types by regulation of numerous signal transduction pathways. The aim of this study was to investigate the biological roles of leptin and the mechanisms attributed to its action in non-small cell lung cancer (NSCLC) cell lines. The expression of leptin was measured by quantitative real-time PCR and western blot in seven NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to leptin knockdown were determined by MTT assay and flow cytometry, respectively. The effect of leptin knockdown on the Notch and JAK/STAT3 signaling pathways was further examined by western blot. Leptin expression was significantly increased in NSCLC cell lines compared with normal human bronchial epithelial cell HBE. Leptin knockdown inhibited cell proliferation and induced apoptosis in NSCLC cell lines through inactivation of the Notch and JAK/STAT3 signaling pathways. Furthermore, gene silencing of Notch signaling with Notch-1 siRNA or inhibition of JAK/STAT3 signaling by JSI-124, an inhibitor of STAT3, resulted in proliferation inhibition and apoptosis induction in NSCLC A549 cells. Our findings suggested that leptin knockdown could become a new approach for the prevention of lung cancer progression, which is likely to be mediated at least partially by inactivation of the Notch and JAK/STAT3 signaling pathways.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Xian-Jie
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Zhong-Xin
authors.initials: ZX
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Dong
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Guo-Yu
authors.identifier: http://orcid.org/0000-0002-3167-1419
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Ming-Fei
authors.initials: MF
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: An
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan Province 475000, China zhangsldoc@163.com.
authors.forename: Shuang-Lin
authors.initials: SL
authors.lastname: Zhang
keywords: Apoptosis; JAK/STAT3; Leptin; Non-small cell lung cancer; Notch; Proliferation