gms | German Medical Science

Background and Aims: Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoAR), called “statins” known for their lowering effect on plasma cholesterol, exerts also antitumor effect. This is in keeping with numerous epidemiologiocal studies demonstrating that statins have protective effect against cancerogenesis (J Clin Oncol 2004; 22: 2388-2394). The role of statins in the prevention and therapy of Barrett adenocarcinoma (BA) has not been investigated so far. The aim of the present study is to analyze 1) the impact of HMG-CoAR inhibitor simvastatin on human Barrett’s adenocarcinoma cell growth; 2) effect of simvastatin on expression of apoptosis related proteins Bax/Bcl-2 and cyclooxygenase-2.

Material and Methods: Barrett’s adenocarcinoma cells (OE-19 cells) were incubated with simvastatin (1µM-30µM). Cell survival was analyzed by MTT assay. The apoptosis rate was evaluated by FACS. The expression of COX-2, Bax and Bcl-2 was analyzed at mRNA and protein level by quantitative RT-PCR and immunoblot.

Results: MTT assay demonstrated a significant and dose-dependent inhibition of OE-19 cell growth. In addition, the FACS analysis showed a significant induction of apoptosis in OE-19 cells incubated with simvastatin. Simvastatin caused also a significant reduction in Bcl-2 expression and increase in Bax expression. In OE-19 cells COX-2 expression was detected and significantly increased by the addition of TNF into the medium, however this effect was significantly attenuated by simvastatin.

Conclusion: 1) Statins possess anti-cancerogenic properties due to induction of apoptosis and inhibition of COX-2, whose products also show pro-apoptocic activity and 2) Clinical trials are necessary to prove the beneficial statin effect in Barrett’s esophagus carcinogenesis.