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Effects of Pembrolizumab and digitoxin in prostate cancer cells
University of Skövde, School of Health and Education.
2019 (English)Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Objective: Digitoxin is a kind of plant-derived cardiac glycoside that is used to treat heart diseases, especially in congestive heart failure or arrhythmia. However, its potentiality presented as an anti-tumour drug remains unexplored. Pembrolizumab, a monoclonal IgG4 antibody, designed to block the PD‒1 receptor have demonstrated anti-tumour effect in patients with melanoma and a wide range of other cancers including renal cell carcinoma, ovarian cancer and Hodgkin lymphoma. The aim of this study was designed to investigate the pharmacological benefits of a digitoxin and pembrolizumab treatment of prostate cancer cell line.

Materials and methods: LNCaP (prostate cancer) cells were seeded and treated with digitoxin, pembrolizumab and a combination of both. The MTS assay was utilized to determine the number of viable cells. PD‒1, PD‒L1 and PD‒L2 genes expression was determined by qPCR (quantitative Polymerase Chain Reaction). Amplex-Red assay was used to measure ROS levels in LNCaP cells.

Results: Cell viability in LNCaP cells was significantly inhibited by digitoxin 10-100 nM and pembrolizumab 0,5-100 mg/l.  A combination treatment with digitoxin 10 nM + pembrolizumab 50 mg/l was statistically significant with decreased cell viability compared to untreated control in LNCaP after 72h of treatment and showed a synergistic effect. The ROS levels was decreased by 25 nM digitoxin + 50 mg/l pembrolizumab and 100 nM digitoxin + 50 mg/l pembrolizumab. qPCR study indicated that digitoxin and pembrolizumab intervention caused an increase in the gene expression of the PD‒1 and PD‒L1/L2 genes.

Conclusions: These findings suggest that digitoxin and pembrolizumab plays a potential anti-tumour role in LNCaP cells in vitro, thus could be used as a new therapy to treat prostate cancer.

Place, publisher, year, edition, pages
2019. , p. 20
Keywords [en]
Prostate Cancer, LNCaP, Digitoxin, Pembrolizumab, MTS-assay, Amplex-red assay, qPCR
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:his:diva-17746OAI: oai:DiVA.org:his-17746DiVA, id: diva2:1356621
Educational program
Biomedicine - Study Programme
Supervisors
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Available from: 2019-10-07 Created: 2019-10-01 Last updated: 2019-10-07Bibliographically approved

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
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  • nn-NO
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  • sv-SE
  • Other locale
More languages
Output format
  • html
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  • asciidoc
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