title: JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer.
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.
authors.affiliation: Department of Obsterics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.|Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Jackson
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Kilgore
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.|Division of Gynecological Oncology, Linyi Tumor Hospital, Linyi, Shandong 276001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA 01843, USA.
authors.forename: Leo Li-Ying
authors.initials: LL
authors.lastname: Chan
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.|Linberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Paola A
authors.initials: PA
authors.lastname: Gehrig
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.|Linberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.|Linberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D001381:Azepines / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis*; D000080864:Lactate Dehydrogenase 5; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009336:Necrosis; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D059467:Transcriptome; D014230:Triazoles / Q000737:chemistry*
chemical_list: C561695:(+)-JQ1 compound; D000970:Antineoplastic Agents; D001381:Azepines; D007527:Isoenzymes; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D014230:Triazoles; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: BRDs inhibitor; c-Myc; metabolism; ovarian cancer; proliferation