title: Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells.
abstract: Ovarian cancer is the most lethal gynecologic malignancy with an overall cure rate of merely 30%. Most patients experience recurrence within 12-24 months of cure and die of progressively chemotherapy-resistant disease. Thus, more effective anti-ovarian cancer therapies are needed. Here, we investigate the possibility of repurposing antibiotic monensin as an anti-ovarian cancer agent. We demonstrate that monensin effectively inhibits cell proliferation, migration and cell cycle progression, and induces apoptosis of human ovarian cancer cells. Monensin suppresses multiple cancer-related pathways including Elk1/SRF, AP1, NFκB and STAT, and reduces EGFR expression in ovarian cancer cells. Monensin acts synergistically with EGFR inhibitors and oxaliplatin to inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Xenograft studies confirm that monensin effectively inhibits tumor growth by suppressing cell proliferation through targeting EGFR signaling. Our results suggest monensin may be repurposed as an anti-ovarian cancer agent although further preclinical and clinical studies are needed.
authors.affiliation: Department of Obstetrics and Gynecology, and Physical Examination, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400046, China.|Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Youlin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, and Physical Examination, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400046, China.|Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhengjian
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|School of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Jixing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Department of Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Department of Orthopaedic Surgery, the Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Lianggong
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Department of Orthopaedic Surgery, Shandong Provincial Hospital and Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Departments of General Surgery, the Affiliated Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Tang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Maryam K
authors.initials: MK
authors.lastname: Mohammed
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Fan
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Fugui
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Obstetrics and Gynecology, and Physical Examination, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400046, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Qi
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, and Physical Examination, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400046, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Tang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008985:Monensin / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D000077150:Oxaliplatin; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D000077150:Oxaliplatin; D008985:Monensin; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1