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

作者：Deng, Youlin; Zhang, Junhui; Wang, Zhongliang; Yan, Zhengjian; Qiao, Min; Ye, Jixing; Wei, Qiang; Wang, Jing; Wang, Xin; Zhao, Lianggong; Lu, Shun; Tang, Shengli; Mohammed, Maryam K.; Liu, Hao; Fan, Jiaming; Zhang, Fugui; Zou, Yulong; Liao, Junyi; Qi, Hongbo; Haydon, Rex C.; Luu, Hue H.; He, Tong-Chuan; Tang, Liangdan

来源：Scientific Reports, 2015, 5(1): 17523.

DOI：10.1038/srep17523

• MEDIATED GROWTH-INHIBITION
• HUMAN OSTEOSARCOMA GROWTH
• HUMAN COLORECTAL-CANCER
• BETA-CATENIN PROTEIN
• TUMOR-GROWTH
• CYCLE ARREST
• STEM-CELLS
• PHASE-II
• CARCINOMA
• APOPTOSIS

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, NF kappa B 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.

• 出版日期2015-12-7
• 单位重庆医科大学; 兰州大学; 武汉大学; 重庆大学; 四川大学; 山东省立医院; 山东大学