학술논문

Sorafenib Triggers Antiproliferative and Pro-Apoptotic Signals in Human Esophageal Adenocarcinoma Cells.
Document Type
Article
Source
Digestive Diseases & Sciences. Dec2008, Vol. 53 Issue 12, p3055-3064. 10p.
Subject
*ANTINEOPLASTIC agents
*ESOPHAGEAL cancer
*ADENOCARCINOMA
*ENZYME inhibitors
*CANCER cell growth regulation
*CANCER cell proliferation
*PATIENTS
Language
ISSN
0163-2116
Abstract
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. [ABSTRACT FROM AUTHOR]