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Front Oncol. 2019 Aug 13;9:754. doi: 10.3389/fonc.2019.00754. eCollection 2019.

SIRT5 Promotes Cisplatin Resistance in Ovarian Cancer by Suppressing DNA Damage in a ROS-Dependent Manner via Regulation of the Nrf2/HO-1 Pathway.

Author information

1
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
2
Department of Hepatopancreatobiliary Surgery, Jilin Province Cancer Hospital, Changchun, China.
3
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
4
Department of Pathology, The First Affiliated Hospital, China Medical University, Shenyang, China.

Abstract

Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance in vitro. Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.

KEYWORDS:

Nrf2/HO-1; SIRT5; drug resistance; ovarian cancer; reactive oxygen species

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