机构：[1]Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.[3]Departments of Surgery, Clinical Laboratory Medicine, Orthopaedic Surgery, Plastic Surgery and Burn, Otolaryngology, Head and Neck Surgery, and Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.[4]Departments of Hepatobiliary & Pancreatic Surgery, Neurosurgery, and Otolaryngology, Head and Neck Surgery, the Affiliated Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.[5]Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, 400016, China.[6]Department of Biochemistry and Molecular Biology, China Three Gorges University School of Medicine, Yichang, 443002, China.[7]Department of Clinical Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, 330031, China.[8]Key Laboratory of Orthopaedic Surgery of Gansu Province, and the Departments of Orthopaedic Surgery and Obstetrics and Gynecology, the First and Second Hospitals of Lanzhou University, Lanzhou, 730030, China.[9]Department of Orthopaedic Surgery, Xiangya Second Hospital of Central South University, Changsha, 410011, China.[10]Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.[11]Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.[12]Department of Clinical Laboratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao, 266061, China.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with <5% five-year survival rate due to late diagnosis, limited treatment options and chemoresistance. There is thus an urgent unmet clinical need to develop effective anticancer drugs to treat pancreatic cancer. Here, we study the potential of repurposing monensin as an anticancer drug for chemo-resistant pancreatic cancer. Using the two commonly-used chemo-resistant pancreatic cancer cell lines PANC-1 and MiaPaCa-2, we show that monensin suppresses cell proliferation and migration, and cell cycle progression, while solicits apoptosis in pancreatic cancer lines at a low micromole range. Moreover, monensin functions synergistically with gemcitabine or EGFR inhibitor erlotinib in suppressing cell growth and inducing cell death of pancreatic cancer cells. Mechanistically, monensin suppresses numerous cancer-associated pathways, such as E2F/DP1, STAT1/2, NFkB, AP-1, Elk-1/SRF, and represses EGFR expression in pancreatic cancer lines. Furthermore, the in vivo study shows that monensin blunts PDAC xenograft tumor growth by suppressing cell proliferation via targeting EGFR pathway. Therefore, our findings demonstrate that monensin can be repurposed as an effective anti-pancreatic cancer drug even though more investigations are needed to validate its safety and anticancer efficacy in pre-clinical and clinical models.
基金：
The reported study was supported in part by research grants from the National Key Research and Development Program
of China (2016YFC1000803 and 2011CB707906), the National Institutes of Health (CA226303 to TCH), the
National Institutes of Health of China (W2017ZWS07 to XL and XW), and the 135 Research Project of West
China Hospital of Sichuan University (XL and XW). XW was a recipient of pre-doctorate scholarship from China
Scholarship Council. This project was also supported in part by The University of Chicago Cancer Center Support
Grant (P30CA014599) and the National Center for Advancing Translational Sciences of the National Institutes
of Health through Grant Number UL1 TR000430. TCH was also supported by the Mabel Green Myers Research
Endowment Fund and The University of Chicago Orthopaedic Surgery Alumni Fund.
第一作者机构：[1]Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
通讯作者：
通讯机构：[1]Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.[2]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
推荐引用方式(GB/T 7714)：
Xin Wang,Xingye Wu,Zhonglin Zhang,et al.Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway[J].SCIENTIFIC REPORTS.2018,8(1):17914.doi:10.1038/s41598-018-36214-5.
APA：
Xin Wang,Xingye Wu,Zhonglin Zhang,Chao Ma,Tingting Wu...&Tong-Chuan He.(2018).Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway.SCIENTIFIC REPORTS,8,(1)
MLA：
Xin Wang,et al."Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway".SCIENTIFIC REPORTS 8..1(2018):17914
