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Inhibition of TrxR1 induces SecTRAPs which promote cytotoxicity and reduce migration in KRAS-driven Lung Cancer
Högskolan i Skövde, Institutionen för hälsovetenskaper.
2020 (Engelska)Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
Abstract [en]

To thrive and proliferate, cancer cells must counteract the oxidative stress, which is upregulated in their environment. To achieve this, antioxidants must be obtained, or their synthesis upregulated. One antioxidant system that is commonly upregulated by cancer cells is the thioredoxin system. Proteins within this system often contain selenium. Two of these, thioredoxin-1 (TRX1) and thioredoxin reductase-1 (TrxR1), are integral in the regulation of ROS. The inhibition of TrxR1 by electrophilic compounds results in selenium compromised thioredoxin reductase derived apoptotic proteins, otherwise known as SecTRAPs. The propagation of these SecTRAPs disrupts the redox balance in the cells resulting in cytotoxic effects, including generation of ROS, membrane instability and cell death. As such, their generation inhibits cell growth and could potentially be therapeutically exploited in future anti-cancer treatments. This study assesses how selenium pre-treatment of lung cancer cells enhances the effect of TrxR1 inhibitors (TRI) such as TRI-1 and auranofin, among others. It measures the effect of inhibition by analysing cell viability, proliferation, and migration. Results indicate that selenium pre-treatment increases the effects of TRI-1 on both migration and proliferation of lung cancer cells. Viability assays indicate 2.5μM as a sub-lethal dose of TRI-1 and auranofin. Effects of TRI-1 at this concentration were used to analyse cytotoxic effects. Migration was reduced in cells with up-regulated TrxR1 synthesis but increased in cells with basal concentrations, while proliferation was decreased by TRI-1 in all cell lines and pre-treatment conditions. Optimization of western blot protocols was also completed for future protein expression analysis.

Ort, förlag, år, upplaga, sidor
2020. , s. 47
Nationell ämneskategori
Biomedicinsk laboratorievetenskap/teknologi
Identifikatorer
URN: urn:nbn:se:his:diva-18683OAI: oai:DiVA.org:his-18683DiVA, id: diva2:1449319
Externt samarbete
Sayin Group, Sahlgrenska Center for Cancer Research
Ämne / kurs
Biomedicin/medicinsk vetenskap
Utbildningsprogram
Biomedicinprogrammet
Handledare
Examinatorer
Tillgänglig från: 2020-06-30 Skapad: 2020-06-30 Senast uppdaterad: 2020-06-30Bibliografiskt granskad

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