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Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway
  1. Xi Zhou, PhD*,,
  2. Hui Li, PhD, MD*,
  3. Yanlan Chai, PhD* and
  4. Zi Liu, MD*
  1. *Department of Radiation Oncology, The First Affiliated Hospital of the Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China; and
  2. Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
  1. Address correspondence and reprint requests to Zi Liu, MD, Department of Radiation Oncology, The First Affiliated Hospital of the Medical College, Xi’an Jiaotong University, 277, Yanta West Road, Xi’an, Shaanxi Province 710061, China. E-mail:


Objectives Leptin has recently been shown to affect cancer proliferation and invasion through multiple pathways. In the current study, we investigated the role of leptin in endometrial carcinoma (EC) apoptosis and the underlying mechanisms of action.

Methods Immunoprecipitation was used to characterize leptin receptor expression in EC lines. The levels of nuclear factor κB–inducing kinase (NIK)/IκB kinase (IKK) signaling proteins were analyzed using Western blot. In addition, Western blot and immunohistochemical analyses were used to detect the hierarchy of these proteins in EC tissues. Quantitative cancer cell apoptosis assay was performed using flow cytometry after incubation of cells with Annexin-V/fluorescein/propidium iodide, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide or staining of cancer cell DNA fragments with propidium iodide.

Results Leptin induced a decrease in apoptosis in Ishikawa and HEC-1A EC cells, partly through nuclear factor κB activation via phosphorylation in the IKK/NIK pathway. Inhibition of IKK or NIK partly neutralized this suppression of apoptosis. Expression levels of leptin receptors (Ob-Rs) and IKK/NIK signaling proteins were higher in poorly and moderately differentiated than in well-differentiated EC tissues, and higher Ob-Rs expression was observed in clinical stages II and III, compared with stage I EC (P = 0.012). High serum leptin concentration displayed mild correlation (r = 0.23, P = 0.035) with degree of EC differentiation.

Conclusions Leptin inhibits EC apoptosis partly through activation of the NIK/IKK pathway in vitro. Ob-Rb overexpression seems to facilitate EC progression.

  • Leptin
  • NIK
  • IKK
  • Apoptosis
  • Endometrial carcinoma

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  • This work was supported by grants from the National Natural Science Foundation of China (General Program, No. 81071838) and Shiyan Biologic Research Foundation of 2015.

  • The authors declare no conflicts of interest.

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