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Down-regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Qiongli Su1,2, Ting Tao1,2, Lei Tang3,4

  • 1Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.

Journal of Cellular and Molecular Medicine
|March 8, 2018
PubMed

Insights

Down-regulating pyruvate kinase M2 (PKM2) enhances the effectiveness of THP chemotherapy for bladder cancer. This approach activates AMPK and inhibits STAT3, improving treatment outcomes in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pyruvate kinase M2 (PKM2) influences glycolysis and anticancer drug sensitivity.
  • THP chemotherapy shows limited efficacy in non-muscle-invasive bladder cancer.
  • Investigating PKM2's role in THP resistance is crucial for improving treatment.

Purpose of the Study:

  • To determine if down-regulating PKM2 can enhance THP efficacy in bladder cancer.
  • To explore the molecular mechanisms underlying PKM2's effect on THP sensitivity.
  • To evaluate the combined effect of PKM2 inhibition and THP in vivo.

Main Methods:

  • PKM2 expression was modulated using inhibitors and siRNA in bladder cancer cell lines.
  • In vitro assays (MTT, colony formation, fluorescence) assessed THP sensitivity.
  • Western blotting analyzed p-AMPK and p-STAT3 levels.
  • An in vivo orthotopic bladder tumor model evaluated treatment efficacy.

Main Results:

  • PKM2 is overexpressed in bladder cancer cells and tissues.
  • Down-regulating PKM2 significantly increased THP sensitivity in vitro.
  • PKM2 inhibition activated AMPK and inhibited STAT3, pathways linked to THP activity.
  • Combination therapy (THP + metformin) completely inhibited tumor growth in vivo.

Conclusions:

  • Down-regulating PKM2 expression is a promising strategy to enhance THP chemotherapy effectiveness.
  • Targeting PKM2 may overcome THP resistance in bladder cancer.
  • This study offers novel insights for optimizing THP-based bladder cancer treatments.
Keywords:
THPPKM2bladder cancerp-AMPKp-STAT3

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