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.
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.
Authors: N Rioux-Leclercq; B Turlin; F Sutherland; N Heresbach; B Launois; J P Campion; M P Ramee Journal: Oncol Rep Date: 1999 Jul-Aug Impact factor: 3.906
Authors: R Adams; M Morgan; S Mukherjee; A Brewster; T Maughan; D Morrey; T Havard; W Lewis; G Clark; S Roberts; L Vachtsevanos; J Leong; R Hardwick; D Carey; T Crosby Journal: Eur J Surg Oncol Date: 2006-11-22 Impact factor: 4.424
Authors: S J Spechler; A H Robbins; H B Rubins; M E Vincent; T Heeren; W G Doos; T Colton; E M Schimmel Journal: Gastroenterology Date: 1984-10 Impact factor: 22.682
Authors: M K Schmidt; L Meurer; B S Volkweis; M I Edelweiss; C C Schirmer; C D P Kruel; R R Gurski Journal: Dis Esophagus Date: 2007 Impact factor: 3.429
Authors: Charles T Miller; Justin R Moy; Lin Lin; Matthew Schipper; Daniel Normolle; Dean E Brenner; Mark D Iannettoni; Mark B Orringer; David G Beer Journal: Clin Cancer Res Date: 2003-10-15 Impact factor: 12.531
Authors: Yanning Liu; Guohua Lou; John T Norton; Chen Wang; Irawati Kandela; Shuai Tang; Nathaniel I Shank; Pankaj Gupta; Min Huang; Michael J Avram; Richard Green; Andrew Mazar; Daniel Appella; Zhi Chen; Sui Huang Journal: FASEB J Date: 2017-08-17 Impact factor: 5.191
Authors: Boris R A Blechacz; Rory L Smoot; Steven F Bronk; Nathan W Werneburg; Alphonse E Sirica; Gregory J Gores Journal: Hepatology Date: 2009-12 Impact factor: 17.425
Authors: Jurjen J Boonstra; Ronald van Marion; David G Beer; Lin Lin; Paula Chaves; Catarina Ribeiro; A Dias Pereira; Lúcia Roque; S Jane Darnton; Nasser K Altorki; David S Schrump; David S Klimstra; Laura H Tang; James R Eshleman; Hector Alvarez; Yutaka Shimada; Herman van Dekken; Hugo W Tilanus; Winand N M Dinjens Journal: J Natl Cancer Inst Date: 2010-01-14 Impact factor: 13.506
Authors: Clemens C Cyran; Bettina Schwarz; Philipp M Paprottka; Steven Sourbron; Jobst C von Einem; Olaf Dietrich; Rabea Hinkel; Dirk A Clevert; Christiane J Bruns; Maximilian F Reiser; Konstantin Nikolaou; Bernd J Wintersperger Journal: Cancer Imaging Date: 2013-12-16 Impact factor: 3.909
Authors: S P D'Angelo; C R Antonescu; D Kuk; L Qin; N Moraco; R C Carvajal; P Chi; M A Dickson; M Gounder; M L Keohan; S Singer; G K Schwartz; W D Tap Journal: Br J Cancer Date: 2013-10-08 Impact factor: 7.640