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Knockdown of PKM2 enhances radiosensitivity of cervical cancer cells

Yanzhu Lin1, Hui Zhai2, Yi Ouyang1

  • 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Cancer Cell International
|May 23, 2019
PubMed
Abstract

Insights

Pyruvate kinase isozyme type M2 (PKM2) is elevated in cervical cancer (CC) and influences treatment response. Inhibiting PKM2 enhances radiosensitivity, offering a potential therapeutic target for CC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pyruvate kinase isozyme type M2 (PKM2) is a key glycolytic enzyme implicated in various cancers.
  • Its role in the radiosensitivity of human cervical cancer (CC) has not been previously established.

Purpose of the Study:

  • To investigate the role of PKM2 in the radiosensitivity of cervical cancer.
  • To determine if PKM2 can be a therapeutic target for enhancing CC radiosensitivity.

Main Methods:

  • Immunohistochemistry was used to assess PKM2 expression in 94 CC patients.
  • Functional assays including colony formation, cell cycle, DNA damage, and apoptosis analyses were performed after PKM2 inhibition and ionizing radiation (IR).
  • Western blotting and immunofluorescence were employed to evaluate protein expression and DNA repair markers.

Main Results:

  • Higher PKM2 expression correlated with a non-complete response (nCR) to treatment in CC patients.
  • PKM2 knockdown combined with IR significantly reduced cell growth, induced apoptosis, and enhanced radiosensitivity.
  • PKM2 inhibition with IR increased DNA damage markers (ATM, γ-H2AX), apoptosis markers (cleaved caspase 3/9), and decreased Bcl2 expression.
  • PKM2 knockdown also suppressed cancer stem cell markers (NANOG, OCT4, SOX2, Bmi1) in vitro.

Conclusions:

  • PKM2 plays a significant role in mediating cervical cancer radiosensitivity.
  • Targeting PKM2 presents a promising strategy to improve radiosensitivity in cervical cancer patients.
Keywords:
ApoptosisCell cycleDouble strand break repairRadiosensitivity

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