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p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells

Mei-Hui Xia1, Xiao-Yu Yan2, Lei Zhou3

  • 1Department of Obstetrics, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.

Journal of Cancer
|February 13, 2020
PubMed

Insights

Overexpressed p62 protein protects ovarian cancer cells from vitamin K3 (VK3) induced oxidative damage by activating the Keap1/Nrf2 signaling pathway, suggesting a new therapeutic target.

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Redox homeostasis imbalance is implicated in chemotherapy resistance in cancer.
  • Vitamin K3 (VK3) shows potential as an anti-tumor agent by promoting reactive oxygen species (ROS) production.

Purpose of the Study:

  • To investigate the role of p62 in mediating resistance to VK3 in ovarian cancer cells.
  • To elucidate the underlying molecular mechanisms involving the Keap1/Nrf2 signaling pathway.

Main Methods:

  • Comparison of VK3 sensitivity between SKOV3 and SKOV3/DDP ovarian cancer cells with differing p62 levels.
  • Analysis of Nrf2 downstream antioxidant gene expression (HO-1, NQO1) following VK3 treatment.
  • Investigation of p62 and Keap1 co-localization.
  • Assessment of apoptosis and gene expression changes upon p62 suppression.

Main Results:

  • SKOV3/DDP cells with high p62 levels exhibited insensitivity to VK3 compared to SKOV3 cells.
  • VK3 treatment upregulated Nrf2 downstream antioxidant genes (HO-1, NQO1) in SKOV3/DDP cells, indicating Nrf2 pathway activation.
  • Co-localization of p62 and Keap1 was observed.
  • Suppression of p62 enhanced VK3-induced apoptosis and downregulated Nrf2, HO-1, and NQO1 expression.

Conclusions:

  • Overexpressed p62 protects ovarian cancer cells against VK3-induced oxidative stress.
  • The protective effect is mediated through the activation of the Keap1/Nrf2 signaling pathway.
  • Targeting p62 may represent a novel strategy to overcome VK3 resistance in ovarian cancer.
Keywords:
Drug resistanceKeap1Nrf2ROSVK3p62

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