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PMID: 18512153 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Digestive diseases and sciences ·Vol. 53 ·No. 12 ·2008-12-00 ·Pages 3055-64

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

Abstract

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. 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. 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. These results support a rational basis for future clinical studies to assess the therapeutic benefit of Sorafenib in esophageal adenocarcinoma.

MeSH Terms
Adenocarcinoma/drug therapy,metabolism,pathology Antineoplastic Agents/pharmacology Apoptosis/drug effects Benzenesulfonates/pharmacology Cell Line, Tumor Cell Proliferation/drug effects Cyclin D1/metabolism Cyclin E/metabolism Esophageal Neoplasms/drug therapy,metabolism,pathology Extracellular Signal-Regulated MAP Kinases/metabolism Humans Niacinamide/analogs & derivatives Phenylurea Compounds Proto-Oncogene Proteins c-akt/metabolism Proto-Oncogene Proteins c-bcl-2/metabolism Proto-Oncogene Proteins c-myc/metabolism Pyridines/pharmacology STAT3 Transcription Factor/metabolism Sorafenib p38 Mitogen-Activated Protein Kinases/metabolism
Chemicals
Antineoplastic Agents Benzenesulfonates Cyclin E MYC protein, human Phenylurea Compounds Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-myc Pyridines STAT3 Transcription Factor STAT3 protein, human Cyclin D1 Niacinamide Sorafenib Proto-Oncogene Proteins c-akt Extracellular Signal-Regulated MAP Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Delgado Jorge-Shmuel
Section of Gastroenterology, Department of Medicine, The University of Chicago Medical Center, MC 4076. 5841 S. Maryland Ave, Chicago, IL, 60637, USA. [email protected]
Mustafi Reba
Yee Jason
Cerda Sonia
Chumsangsri Anusara
Dougherty Urszula
Lichtenstein Lev
Fichera Alessandro
Bissonnette Marc
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Article Info
Journal
Digestive diseases and sciences
Abbr.
Dig Dis Sci
ISSN
0163-2116
DOI
10.1007/s10620-008-0294-y
Email
[email protected]
Published
2008-12-00
Epub
2008-00-30
Pages
3055-64
Language
English
Region
United States
NLM ID
7902782
Subset
IM
Grants
NCI NIH HHS · CA036745 · United States
NIDDK NIH HHS · P30DK42086 · United States
External Links
PubMed source DOI: 10.1007/s10620-008-0294-y View journal details
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