Publikationsserver der Universitätsbibliothek Marburg
Titel:Die Inhibition des Transkriptionsfaktors Snail durch PEG und GN25 in Zelllinien des humanen duktalen Adenokarzinoms des Pankreas (SUIT-2/007 und SUIT-2/028)
Autor:Dengler, Janina
Weitere Beteiligte: Fendrich, Volker (Prof. Dr.)
Veröffentlicht:2018
URI:https://archiv.ub.uni-marburg.de/diss/z2018/0120
URN: urn:nbn:de:hebis:04-z2018-01206
DOI: https://doi.org/10.17192/z2018.0120
DDC: Medizin
Publikationsdatum:2018-06-11
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Pankreaskarzinom, Snail

Zusammenfassung:
Hintergrund: Die Gründe für die schlechte Prognose des duktalen Pankreaskarzinoms sind vor allem auch seine Resistenz gegen Chemotherapeutika und seine frühe Metastasierung. Hierbei spielt die epithelial-mesenchymale Transition (EMT) eine entscheidende Rolle, die mit dem Verlust von Zell-Zell-Verbindungen, der Zellpolarität und der Expression von E-Cadherin einhergeht. Ein wichtiger Mediator der EMT ist der Transkriptionsfaktor Snail, der über verschiedene Signalwege die Expression von E-Cadherin hemmt. Therapieansätze zur Hemmung von Snail sind derzeit jedoch noch kaum vorhanden. In dieser Arbeit untersuchten wir in vitro die Inhibiton von Snail durch PEG und GN25 in den Pankreaskarzinomzelllinien Suit2-007 und Suit2-028. Material und Methoden: Für die Untersuchungen wurden die Zelllinien Suit-2 bzw. ihre Subzelllinien Suit-2/007 und Suit-2/028. Suit-2/007 (Zelllinie mit hohem Metastasierungspotential) und Suit-2/028 (Zelllinie mit geringem Metastasierungspotential) verwendet. Kultiviert wurden die Zellen in RPMI/10%FCS-Medium. Nach Austestung der erforderlichen Zellzahl erfolgte die Beimpfung der Zelllinien mit den Inhibitoren PEG und GN25 über je 24h, 72h und 144h und mit verschiedenen Konzentrationen (PEG: 5% und 10%; GN:25 0,5 µM, 1µM, 2µM, 4µM, 5µM, 6µM, 8µM und 10µM). Nach den entsprechenden Zeiträumen erfolgte die Messung der vitalen Zellen mittels MTT-Assay im ELISA-Reader bei 570nm und 630nm. Ergebnisse: Die Inhibition der Zelllinien mit PEG zeigte eine dosisabhängige Wachstumshemmung beider Zelllinien, wobei eine signifikante Verminderung der Zellzahl erst bei einer Inkubationszeit von 144 Stunden festgestellt werden konnte (p<0,001). Der Effekt auf die beiden unterschiedlichen Zelllinien war vergleichbar. Noch deutlicher war die Inhibition der Zellen durch die Beimpfung mit GN25. Hier zeigte sich jedoch bereits eine deutliche Wachstumshemmung nach 72 Stunden Inkubation, welche nach 144 Stunden noch immer zu beobachten war (p<0,001). Zudem zeigte sich ein hoch signifikanter Abfall der Zellkonzentration ab einer Dosis von 5µM (p< 0,001). Auch hier war die Wirkung auf beide Zelllinien vergleichbar. Schlussfolgerung: PEG und GN25 verursachen eine signifikante dosisabhängige Inhibition von Snail beim Pankreaskarzinom in vitro, wobei die Wachstumshemmung der Zellen durch GN25 deutlich schneller und in geringeren Dosen auftrat, als bei der Hemmung mit PEG. PEG und insbesondere GN25 stellen potentielle neue Ansätze für die Therapie des metastasierten Pankreaskarzinoms dar.

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