ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III NAD+ dependent histone deacetylases (HDACs), has been reported to be involved in regulating cancer hallmarks including drug response. In this study, we aimed to identify the role of SIRT2 in oxidative stress and cisplatin response in cancer. Two ovarian cancer cell lines featuring different sensitivities to cisplatin were used in this study. We found different expression patterns of SIRT2 in cisplatin-sensitive (A2780/S) and cisplatin-resistant (A2780/CP) cancer cells with cisplatin treatment, where SIRT2 expression was augmented only in A2780/S cells. Furthermore, cisplatin-induced ROS generation was responsible for the upregulation of SIRT2 in A2780/S cells, whereas overexpression of SIRT2 significantly enhanced the sensitivity of cisplatin-resistant counterpart cells to cisplatin. Our study proposes that targeting SIRT2 may provide new strategies to potentiate platinum-based chemotherapy in ovarian cancer patients.

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Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients

Gynecologic Oncology ◽

10.1016/j.ygyno.2009.04.024 ◽

2009 ◽

Vol 114 (2) ◽

pp. 253-259 ◽

Cited By ~ 113

Author(s):

Ram Eitan ◽

Michal Kushnir ◽

Gila Lithwick-Yanai ◽

Miriam Ben David ◽

Moshe Hoshen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Expression Patterns ◽

Microrna Expression ◽

Platinum Based Chemotherapy

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Metabolic Regulation of Ovarian Cancer Cell Death

10.21236/ada570124 ◽

2012 ◽

Author(s):

Sally Kornbluth

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cell ◽

Metabolic Regulation ◽

Ovarian Cancer Cell ◽

Cancer Cell Death

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Metabolic Regulation of Ovarian Cancer Cell Death

10.21236/ada597625 ◽

2013 ◽

Author(s):

Sally Kornbluth

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cell ◽

Metabolic Regulation ◽

Ovarian Cancer Cell ◽

Cancer Cell Death

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Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-017-4563-x ◽

2017 ◽

Vol 297 (1) ◽

pp. 153-159 ◽

Cited By ~ 12

Author(s):

Chuchu Zhao ◽

Saisai Li ◽

Menghuang Zhao ◽

Haiyan Zhu ◽

Xueqiong Zhu

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Mismatch Repair Genes ◽

Dna Mismatch ◽

Dna Mismatch Repair Genes ◽

Platinum Based Chemotherapy ◽

Repair Genes

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Abstract TMIM-073: THE COMBINATION OF INTERFERONS ALPHA AND GAMMA AND MONOCYTES INDUCES OVARIAN CANCER CELL DEATH AND PROVIDE A RATIONALE FOR A NOVEL, ONGOING, IMMUNOTHERAPY PHASE 1 CLINICAL TRIAL

10.1158/1557-3265.ovcasymp18-tmim-073 ◽

2019 ◽

Author(s):

Daniel S. Green ◽

Chase L. Johnson ◽

Chen-Feng Qi ◽

Kevin W. Tosh ◽

Olena Kamenyeva ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Trial ◽

Cell Death ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Phase 1 ◽

Phase 1 Clinical Trial ◽

Cancer Cell Death

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Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: Implications for therapy

Cancer Biology & Therapy ◽

10.4161/cbt.6.5.4007 ◽

2007 ◽

Vol 6 (5) ◽

pp. 795-801 ◽

Cited By ~ 63

Author(s):

Dineo Khabele ◽

Deok-Soo Son ◽

Angelika K. Parl ◽

Gary L. Goldberg ◽

Leonard H. Augenlicht ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Growth ◽

Gene Silencing ◽

Cancer Cell ◽

Histone Deacetylases ◽

Ovarian Cancer Cell ◽

Class I ◽

Cancer Cell Growth ◽

Drug Induced ◽

Or Gene

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Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis

Frontiers in Genetics ◽

10.3389/fgene.2020.597467 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tao Li ◽

Jie Yang ◽

Ben Yang ◽

Guoqing Zhao ◽

Hai Lin ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Cell Biology ◽

Ovarian Cancer Cell ◽

Pain Treatment ◽

Ovarian Cancer Cells ◽

Cancer Cell Growth ◽

Ovarian Cancer Cell Lines ◽

Rna Immunoprecipitation

Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Moreover, ketamine induced ovarian cancer cell cycle arrest, apoptosis, and inhibited colony formation capacity. Since lncRNAs have been identified as key regulators of cancer development, we performed bioinformatics analysis of a GEO dataset and found fourteen significantly altered lncRNAs in ovarian cancer patients. We then investigated the effect of ketamine on these lncRNAs, and found that ketamine regulated the expression of lncRNA PVT1. Mechanistically, ketamine regulated P300-mediated H3K27 acetylation activation in the promoter of PVT1. Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Our study revealed that ketamine could be a potential therapeutic strategy for ovarian cancer patients.

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