p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system

  • Authors:
    • Meihui Xia
    • Huimei Yu
    • Shuang Gu
    • Ye Xu
    • Jing Su
    • Hongyan Li
    • Jinsong Kang
    • Manhua Cui
  • View Affiliations

  • Published online on: September 24, 2014     https://doi.org/10.3892/ijo.2014.2669
  • Pages: 2341-2348
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Abstract

The mechanisms underlying cisplatin resistance in tumors are not fully understood. Previous studies have reported that cellular resistance to oxidative stress is accompanied by resistance to cisplatin. However, the relationship between the resistance to oxidative stress and cisplatin drug resistance in human ovarian cancer cells (HOCCs) is not clear. Here, we reveal a critical role for the multifunctional protein p62/SQSTM1 in cisplatin resistance in human ovarian cancer cells (HOCCs). p62/SQSTM1 (sequestosome 1) plays important roles in cell differentiation, proliferation and as an antiapoptotic molecule. We found that cisplatin-resistant SKOV3/DDP cells express much higher levels of p62 than do cisplatin-sensitive SKOV3 cells. The protein p62 can activate the Keap1-Nrf2-ARE signaling pathway and induce the expression of antioxidant genes in SKOV3/DDP cells. Knockdown of p62 resensitizes SKOV3/DDP cells to cisplatin. Collectively, our data indicate that cisplatin resistance in HOCCs is partially attributable to their high expression of p62, which plays an important role in preventing ROS stress-induced apoptosis by regulating the Keap1-Nrf2-ARE signaling pathway.
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December-2014
Volume 45 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Xia M, Yu H, Gu S, Xu Y, Su J, Li H, Kang J and Cui M: p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system. Int J Oncol 45: 2341-2348, 2014
APA
Xia, M., Yu, H., Gu, S., Xu, Y., Su, J., Li, H. ... Cui, M. (2014). p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system. International Journal of Oncology, 45, 2341-2348. https://doi.org/10.3892/ijo.2014.2669
MLA
Xia, M., Yu, H., Gu, S., Xu, Y., Su, J., Li, H., Kang, J., Cui, M."p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system". International Journal of Oncology 45.6 (2014): 2341-2348.
Chicago
Xia, M., Yu, H., Gu, S., Xu, Y., Su, J., Li, H., Kang, J., Cui, M."p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system". International Journal of Oncology 45, no. 6 (2014): 2341-2348. https://doi.org/10.3892/ijo.2014.2669