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

Jorge Shmuel Delgado, Reba Mustafi, Jason Yee, Sonia Cerda, Anusara Chumsangsri, Urszula Dougherty, Lev Lichtenstein, Alessandro Fichera, Marc Bissonnette

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)3055-3064
Number of pages10
JournalDigestive Diseases and Sciences
Volume53
Issue number12
DOIs
StatePublished - 1 Dec 2008
Externally publishedYes

Keywords

  • Barrett's esophagus
  • Cyclin D1
  • Cyclin E
  • Esophageal adenocarcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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