Leptin promotes human glioblastoma growth through activating Signal Transducers and Activators of Transcription 3 signaling

Brain Res Bull. 2012 Feb 10;87(2-3):274-9. doi: 10.1016/j.brainresbull.2011.11.007. Epub 2011 Nov 23.

Abstract

Leptin plays an important role in cancer development and progression. However, its role on human glioblastoma cell line U87 growth and the underlying mechanism remains unexplored. In this study, we assessed the effect of leptin on U87 cells proliferation in vitro and in vivo, elucidating its underlying mechanism. The results showed that leptin significantly promoted U87 tumor cells growth in a time-and-dose-dependent manner. Leptin increased cell DNA synthesis and promoted G(0)/G(1) phase to S phase transition, but without any influence on cell apoptosis. In addition, leptin treatment resulted in phosphorylation of Signal Transducers and Activators of Transcription 3 (STAT3) on Tyr705, the key transcription factor in Janus-Activated Kinase (JAK)/STAT3 signaling pathway. All the data suggest that the JAK/STAT3 signaling pathway may be involved in promoting U87 glioblastoma growth mediated by leptin, which may be a target for anti-neoplastic treatments for glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioblastoma / pathology
  • Humans
  • Leptin / pharmacology*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Time Factors
  • Transcriptional Activation / drug effects*

Substances

  • Leptin
  • RNA, Messenger
  • RNA, Small Interfering
  • STAT3 Transcription Factor