J Cancer 2020; 11(6):1299-1307. doi:10.7150/jca.34423

Research Paper

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

Mei-hui Xia1, Xiao-yu Yan2, Lei Zhou3, Long Xu2, Li-chao Zhang2, Hao-wei Yi2, Jing Su2✉

1. Department of Obstetrics, the First Bethune Hospital of Jilin University, Changchun, Jilin, China.
2. Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
3. Department of Pathology, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China.

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Xia Mh, Yan Xy, Zhou L, Xu L, Zhang Lc, Yi Hw, Su J. p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells. J Cancer 2020; 11(6):1299-1307. doi:10.7150/jca.34423. Available from http://www.jcancer.org/v11p1299.htm

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Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.

Keywords: p62, VK3, ROS, Drug resistance, Nrf2, Keap1