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ID: 281 (Conflict of Interest: K)

Expressions- und Aktivitätsanalyse von Histon-Deacetylasen in Zellen des ösophagealen Adenokarzinoms

R.Thieme1, R.Nowotny1, R.Maly1, O.Lyros1, B.Jansen-Winkeln1, F. K.Hansen2, I.Gockel1
1Universitätsklinikum Leipzig AöR, Leipzig
2Universität Leipzig, Leipzig

Einleitung

The response of EAC to common chemotherapeutic regimes is relatively low and the 5-years-survival is poor. Histone deacetylases (HDAC) are involved in the epigenetic regulation of gene expression. Inhibition of this enzyme class promises novel therapeutic treatment options.

Material und Methoden

We characterized the Zn2+-dependent HDACs in esophageal adenocarcinoma cells in vitro (OE-33, OE-19). Proliferation assays were carried out to determine cell response to three experimental HDAC inhibitors in comparison to Vorinostat. Both, the endogenous HDAC activity and activity under HDACi treatment and the expression of the senescence marker p21 were analyzed.

 

Ergebnisse

We detected a variable expression of the different HDACs. Vorinostat treatment of OE33 and OE19 cells showed an inhibition of proliferation (IC50 of 1.1µM and 1.8µM). In contrast, the experimental HDACi DDK137 revealed an increased inhibition of proliferation (IC50 of 0.4µM and 0.6µM), HDAC activity and increased induction of apoptosis. p21 showed a cell line, time and inhibitor specific increase. The highest increase was determined in OE33 cells (2.5fold) by DDK137 after 48h, while Vorinostat was not able to induce p21, neither in OE33 nor in OE19 cells.

Schlussfolgerung

From the diversity in the potency of HDACi, further studies are necessary to evaluate the significance of HDACs in tumor development and progression of Barrett’s carcinoma and to question, whether or not HDACi can increase chemosensitivity for agents, such as 5-FU and platin compounds by inducing apoptosis and regulating genes involved in cell cycle control.