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Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis
Oncotarget
  • Q. Liu
  • W. Yuan
  • D. Tong
  • G. Liu
  • W. Lan
  • Diangzheng Zhang, Philadelphia College of Osteopathic Medicine
  • H. Xiao
  • Y. Zhang
  • J. Yang
  • J. Zhang
Document Type
Article
Publication Date
1-1-2016
Disciplines
Abstract
Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions. Metformin also can arrest bladder cancer cells in G1/S phases, which subsequently leads to apoptosis. And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models. More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3. In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis.
Comments

This article was published in Oncotarget, Volume 7, Issue 19, Pages 28235-28246.

The published version is available at http://dx.doi.org/10.18632/oncotarget.8595 .

Copyright © 2016 the authors.

Citation Information
Q. Liu, W. Yuan, D. Tong, G. Liu, et al.. "Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis" Oncotarget Vol. 7 Iss. 19 (2016) p. 28235 - 28246
Available at: http://works.bepress.com/dianzheng_zhang/43/