Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells
0301 basic medicine
Organoplatinum Compounds
Antineoplastic Agents
Apoptosis
Article
Receptor, IGF Type 1
03 medical and health sciences
Cell Movement
Cell Line, Tumor
Humans
Monensin
Protein Kinase Inhibitors
Cell Proliferation
Ovarian Neoplasms
Wound Healing
0303 health sciences
Cell Cycle
Drug Synergism
16. Peace & justice
Anti-Bacterial Agents
3. Good health
ErbB Receptors
Oxaliplatin
HEK293 Cells
Female
Signal Transduction
DOI:
10.1038/srep17523
Publication Date:
2015-12-07T09:59:25Z
AUTHORS (23)
ABSTRACT
AbstractOvarian 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.
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