Dabigatran Potentiates Gemcitabine-Induced Growth Inhibition of Pancreatic Cancer in Mice
| العنوان: | Dabigatran Potentiates Gemcitabine-Induced Growth Inhibition of Pancreatic Cancer in Mice |
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| المؤلفون: | Kun Shi, Joost Daalhuisen, C. Arnold Spek, Helene Damhofer, Marieke S. ten Brink, Dick J. Richel |
| المساهمون: | Center of Experimental and Molecular Medicine, CCA - Cancer biology and immunology, Other departments |
| المصدر: | Molecular medicine (Cambridge, Mass.), 23, 13-23. Feinstein Institute for Medical Research Molecular Medicine, Vol 23, Iss 1, Pp 13-23 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Dabigatran, lcsh:Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Thrombin, Pancreatic cancer, Genetics, medicine, lcsh:QD415-436, Molecular Biology, Genetics (clinical), Tumor microenvironment, business.industry, lcsh:RM1-950, medicine.disease, Primary tumor, Gemcitabine, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, chemistry, Direct thrombin inhibitor, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Growth inhibition, business, medicine.drug, Research Article |
| الوصف: | Pancreatic cancer is one of the most lethal solid malignancies, with few treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives the progression and induces the chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we address the effects of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth, whereas it significantly increased tumor dissemination throughout the peritoneal cavity. Increased dissemination was accompanied by intratumoral bleeding and increased numbers of aberrant and/or collapsed blood vessels in the primary tumors. In combination with gemcitabine, dabigatran treatment limited primary tumor growth, did not induce bleeding complications and prevented tumor cell dissemination. Dabigatran was, however, not as efficient as genetic ablation of PAR-1 in our previous study, suggesting that thrombin is not the main PAR-1 agonist in the setting of pancreatic cancer. Overall, we show that dabigatran potentiates gemcitabine-induced growth inhibition of pancreatic cancer but does not affect primary tumor growth when used as monotherapy. |
| اللغة: | English |
| تدمد: | 1076-1551 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0dea92fc79d085ef9016a85a77076bed https://doi.org/10.2119/molmed.2016.00214 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0dea92fc79d085ef9016a85a77076bed |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 10761551 |
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