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

被引：29

作者：

Xia, Mei-hui ^{[1
]}

Yan, Xiao-yu ^{[2
]}

Zhou, Lei ^{[3
]}

Xu, Long ^{[2
]}

Zhang, Li-chao ^{[2
]}

Yi, Hao-wei ^{[2
]}

Su, Jing ^{[2
]}

机构：

[1] Jilin Univ, Bethune Hosp 1, Dept Obstet, Changchun, Jilin, Peoples R China

[2] Jilin Univ, Dept Pathophysiol, Coll Basic Med Sci, Minist Educ,Key Lab Pathobiol, 126 Xinmin St, Changchun 130021, Jilin, Peoples R China

[3] Changchun Univ Chinese Med, Affiliated Hosp, Dept Pathol, Changchun 130021, Peoples R China

来源：

JOURNAL OF CANCER | 2020年 / 11卷 / 06期

基金：

中国国家自然科学基金;

关键词：

p62; VK3; ROS; Drug resistance; Nrf2; Keap1; TRANSCRIPTION FACTOR NRF2; CISPLATIN RESISTANCE; ANTIOXIDANT RESPONSE; TARGET GENE; P62/SQSTM1; VITAMIN-K3; STRESS; CHEMORESISTANCE; MECHANISMS; EXPRESSION;

D O I：

10.7150/jca.34423

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1299 / 1307

页数：9

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