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In vitro treatment of Pancreatic Ductal Adenocarcinoma cancer (CFPAC-1) by Digitoxin and Pembrolizumab (Keytruda): An experimental study to investigate the anti-cancer effect of Digitoxin and Pembrolizumab on Pancreatic Ductal Adenocarcinoma
University of Skövde, School of Health and Education. privat.
2019 (English)Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Pancreatic Ductal Adenocarcinomas (PDAC) is the fourth deadliest cancer in western countries, 95% of diagnosed patients have 1 to 5 months of survival chance, and only 5% survive 5 years. The high morbidity and mortality can be due to late diagnosis which leads to a poorly prognosis, most of PDAC patients are diagnosed metastatic stages, with median age of 60-70 years old. Risk factors that are associated with tumorigenesis of PDAC: environmental factor, genetic mutation, elevated Reactive Oxygen Species (ROS), suppression of Programmed death receptor (PD-1) by PD-ligands (PD-L1 and PD-L2). The aim of the study was to investigate if proliferation of CFPAC-1 cells from PDAC, grown in vitro could be inhibited by Digitoxin, to investigate the role of Digitoxin on ROS production in CFPAC-1, and also investigate if combination of Digitoxin and Pembrolizumab leads to synergistic effect. The expression of PD-1 and PD-L1/L2 were investigated by Quantitative Polymerase Chain Reaction (qPCR). The MTS-assay was used to determine the cell viability, the Amplex-Red-assay was used to investigate the ROS level in CFPAC-1. Found was that the cell proliferation was significantly inhibited by Digitoxin at 10-100nM concentration, and also by the combination of Digitoxin with Pembrolizumab. The ROS production was upregulated by 100nM Digitoxin and down-regulated by 25nM Digitoxin and combination of Digitoxin with Pembrolizumab. The expression of PD-1, PD-L1/L2 were upregulated by 10-and-50mg/L Pembrolizumab, and by the combination of Pembrolizumab and 100nM Digitoxin. These findings suggest that Digitoxin has an anti-proliferation effect and can be used in combination with Pembrolizumab as anti-cancer therapy for PDAC.

Place, publisher, year, edition, pages
2019. , p. 24
Keywords [en]
Pancreatic Ductal Adenocarcinoma, CFPAC-1, In vitro treatment, Digitoxin, Pembrolizumab, MTS-assay, Amplex-red-assay, qPCR
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:his:diva-17312OAI: oai:DiVA.org:his-17312DiVA, id: diva2:1331832
Subject / course
Biomedicine/Medical Science
Educational program
Biomedicine - Study Programme
Supervisors
Examiners
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved

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