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

被引：63

作者：

Deng, Youlin ^{[1
,2
,3
]}

Zhang, Junhui ^{[1
,2
,3
]}

Wang, Zhongliang ^{[3
,4
,5
]}

Yan, Zhengjian ^{[3
,4
,5
]}

Qiao, Min ^{[3
,4
,5
]}

Ye, Jixing ^{[3
,6
]}

Wei, Qiang ^{[3
,4
,5
]}

Wang, Jing ^{[3
,4
,5
]}

Wang, Xin ^{[3
,7
]}

Zhao, Lianggong ^{[3
,8
]}

Lu, Shun ^{[3
,9
,10
]}

Tang, Shengli ^{[3
,11
]}

Mohammed, Maryam K. ^{[3
]}

Liu, Hao ^{[3
,4
,5
]}

Fan, Jiaming ^{[3
,4
,5
]}

Zhang, Fugui ^{[3
,4
,5
]}

Zou, Yulong ^{[3
,4
,5
]}

Liao, Junyi ^{[3
,4
,5
]}

Qi, Hongbo ^{[1
,2
]}

Haydon, Rex C. ^{[3
]}

Luu, Hue H. ^{[3
]}

He, Tong-Chuan ^{[3
,4
,5
]}

Tang, Liangdan ^{[1
,2
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400046, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Phys Examinat, Chongqing 400046, Peoples R China

[3] Univ Chicago, Med Ctr, Mol Oncol Lab, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA

[4] Chongqing Med Univ, Key Lab Diagnost Med, Minist Educ, Chongqing 400016, Peoples R China

[5] Chongqing Med Univ, Affiliated Hosp, Chongqing 400016, Peoples R China

[6] Chongqing Univ, Sch Bioengn, Chongqing 400044, Peoples R China

[7] Sichuan Univ, West China Hosp, Dept Surg, Chengdu 610041, Peoples R China

[8] Lanzhou Univ, Affiliated Hosp 2, Dept Orthopaed Surg, Lanzhou 730000, Gansu, Peoples R China

[9] Shandong Prov Hosp, Dept Orthopaed Surg, Jinan 250012, Peoples R China

[10] Shandong Univ, Sch Med, Jinan 250012, Peoples R China

[11] Wuhan Univ, Affiliated Zhongnan Hosp, Dept Gen Surg, Wuhan 430071, Peoples R China

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

MEDIATED GROWTH-INHIBITION; HUMAN OSTEOSARCOMA GROWTH; TUMOR-GROWTH; CYCLE ARREST; PHASE-II; DIFFERENTIATION; CARCINOMA; PROTEIN; COMBINATION; METASTASIS;

D O I：

10.1038/srep17523

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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