Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Xin Wang, Xingye Wu, Zhonglin Zhang, Chao Ma, Tingting Wu, Shengli Tang, Zongyue Zeng, Shifeng Huang, Cheng Gong, Chengfu Yuan, Linghuan Zhang, Yixiao Feng, Bo Huang, Wei Liu, Bo Zhang, Yi Shen, Wenping Luo, Xi Wang, Bo Liu, Yan Lei, Zhenyu Ye, Ling Zhao, Daigui Cao, Lijuan Yang, Xian Chen, Rex C. Haydon, Hue H. Luu, Bing Peng, Xubao Liu, Tong-Chuan He

ABSTRACT

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. More... »

PAGES

17914

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-36214-5

DOI

http://dx.doi.org/10.1038/s41598-018-36214-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110537229

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30559409


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570 Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, 60637, Chicago, IL, USA
571 rdf:type schema:Organization
 




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