Sorafenib Triggers Antiproliferative and Pro-Apoptotic Signals in Human Esophageal Adenocarcinoma Cells |
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Authors: | Jorge-Shmuel Delgado Reba Mustafi Jason Yee Sonia Cerda Anusara Chumsangsri Urszula Dougherty Lev Lichtenstein Alessandro Fichera Marc Bissonnette |
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Affiliation: | Section of Gastroenterology, Department of Medicine, The University of Chicago Medical Center, MC 4076. 5841 S. Maryland Ave, Chicago, IL, 60637, USA. delgado@bgu.ac.il |
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Abstract: | BACKGROUND AND PURPOSE: Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We investigated the effects of Sorafenib, a multifunctional kinase inhibitor, on several growth regulatory pathways that control cell growth and survival in SEG-1 cells derived from Barrett's adenocarcinoma. METHODS: SEG-1 cells were exposed to acidified medium or taurocholic acid, with and without pre-incubation with Sorafenib. Cyclin D1 and E, c-Myc, and Bcl-2 expression levels as well as STAT3 activations were determined by Western blotting. Cyclin D1 mRNA was measured by real-time PCR. Apoptosis was assessed by TUNEL assay. RESULTS: Sorafenib significantly inhibited SEG-1 cell proliferation stimulated by acid or bile acid treatments and reduced cell survival. This drug significantly reduced the up-regulations of cyclin D1, cyclin E, c-Myc, and Bcl-2 as well as the activation of STAT3 in SEG-1 cells. CONCLUSIONS: These results support a rational basis for future clinical studies to assess the therapeutic benefit of Sorafenib in esophageal adenocarcinoma. |
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Keywords: | Sorafenib Cyclin D1 Cyclin E Barrett’ s esophagus Esophageal adenocarcinoma |
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