Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells

• DOI: 10.1038/srep17523
• Publication Date: 2015-12-07T09:59:25Z
• Authors: Youlin Deng; Junhui Zhang; Zhongliang Wang; Zhengjian Yan; Min Qiao; Jixing Ye; Qiang Wei; Jing Wang; Xin Wang; Lianggong Zhao; Shun Lu; Shengli Tang; Maryam K. Mohammed; Hao Liu; Jiaming Fan; Fugui Zhang; Yulong Zou; Junyi Liao; Hongbo Qi; Rex C. Haydon; Hue H. Luu; Tong-Chuan He; Liangdan Tang
• Keywords: 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

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.