Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis

Qiuli Liu1, Wenqiang Yuan1, Dali Tong1

  • 1Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.

Oncotarget
|April 9, 2016
PubMed

Insights

Metformin inhibits bladder cancer progression by reducing cancer stem cells (CSCs). This drug targets the COX2/PGE2/STAT3 pathway, offering a new approach for bladder cancer treatment.

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology
  • Pharmacology

Background:

  • Cancer stem cells (CSCs) drive tumor initiation, metastasis, and drug resistance in various cancers, including bladder cancer.
  • Metformin shows potential in repressing CSCs in other cancers, but its effect on bladder cancer CSCs is not well understood.

Purpose of the Study:

  • To investigate the effects of metformin on bladder cancer progression and cancer stem cell (CSC) repopulation.
  • To elucidate the underlying molecular mechanisms, specifically the role of the COX2/PGE2/STAT3 pathway.

Main Methods:

  • Utilized the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model.
  • Assessed metformin's impact on tumor progression, cell cycle arrest, apoptosis, and CSC markers (CK14+, OCT3/4+).
  • Investigated the inhibition of COX2, PGE2, and STAT3 activation.

Main Results:

  • Metformin repressed bladder cancer progression from dysplasia to invasive lesions.
  • Metformin induced G1/S phase arrest and apoptosis in bladder cancer cells.
  • Metformin reduced CSC populations (CK14+, OCT3/4+) and inhibited the COX2/PGE2/STAT3 pathway.

Conclusions:

  • Metformin effectively inhibits bladder cancer progression and CSC repopulation.
  • The anticancer effects of metformin are mediated through the inhibition of the COX2/PGE2/STAT3 signaling axis.
  • This study provides the first systemic evidence of metformin's mechanism against bladder cancer via CSC inhibition.

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