Sorafenib triggers antiproliferative and pro-apoptotic signals in human esophageal adenocarcinoma cells.

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Delgado JS, Mustafi R, Yee J, Cerda S, Chumsangsri A, Dougherty U, Lichtenstein L, Fichera A, Bissonnette M

Sorafenib triggers antiproliferative and pro-apoptotic signals in human esophageal adenocarcinoma cells.

Dig Dis Sci. 2008 Dec;53(12):3055-64. doi: 10.1007/s10620-008-0294-y. Epub 2008 May 30.

PubMed ID

18512153 [ View in PubMed

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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.