Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-36214-5
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Funding
- National Key Research and Development Program of China [2016YFC1000803, 2011CB707906]
- National Institutes of Health [CA226303]
- National Institutes of Health of China [W2017ZWS07]
- 135 Research Project of West China Hospital of Sichuan University
- China Scholarship Council
- University of Chicago Cancer Center Support Grant [P30CA014599]
- National Center for Advancing Translational Sciences of the National Institutes of Health [UL1 TR000430]
- Mabel Green Myers Research Endowment Fund
- University of Chicago Orthopaedic Surgery Alumni Fund
- NATIONAL CANCER INSTITUTE [P30CA014599, R21CA226303] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000430] Funding Source: NIH RePORTER
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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.
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