Oncotarget

Research Papers:

JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer*

Haifeng Qiu _, Amanda L. Jackson, Joshua E. Kilgore, Yan Zhong, Leo Li-Ying Chan, Paola A. Gehrig, Chunxiao Zhou and Victoria L. Bae-Jump

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Oncotarget. 2015; 6:6915-6930. https://doi.org/10.18632/oncotarget.3126

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Abstract

Haifeng Qiu1,2, Amanda L. Jackson2, Joshua E. Kilgore2, Yan Zhong2,3, Leo Li-Ying Chan4, Paola A. Gehrig2,5, Chunxiao Zhou2,5, Victoria L. Bae-Jump2,5

1Department of Obsterics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

2Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

3Division of Gynecological Oncology, Linyi Tumor Hospital, Linyi, Shandong 276001, China

4Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA 01843, USA

5Linberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

*This work was partially presented at the 2013 Annual Meeting of the American Association for Cancer Research (AACR), Washington DC

Correspondence to:

Victoria L. Bae-Jump, e-mail: vbae@unch.unc.edu

Chunxiao Zhou, e-mail: czhou@med.unc.edu

Keywords: Ovarian cancer, BRDs inhibitor, c-Myc, Metabolism, Proliferation

Received: November 13, 2014     Accepted: January 09, 2015     Published: February 05, 2015

ABSTRACT

Amplification and overexpression of c-Myc is commonly seen in human ovarian cancers, and this could be a potentially novel therapeutic target for this disease. JQ1, a selective small-molecule BET bromodomain (BRDs) inhibitor, has been found to suppress tumor progression in several cancer cell types. Using ovarian cancer cell lines, a transgenic mouse model, and primary cell cultures from human ovarian cancer tissues, we demonstrated that JQ1 significantly suppressed cellular proliferation and induced cell cycle arrest and apoptosis in ovarian cancer cells and mouse model via targeting c-Myc. In addition, JQ1 had multiple influences on cancer metabolism, particularly in the aerobic glycolysis pathway. JQ1 reduced both the activity and phosphorylation of LDHA, inhibited lactate production, and decreased the energy supply to ovarian cancer cell lines and tumors. Taken together, our findings suggest that JQ1 is an efficacious anti-tumor agent in ovarian cancer that is associated with cell cycle arrest, induction of apoptosis and alterations of metabolism.


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