Sorafenib Triggers Antiproliferative and Pro-Apoptotic Signals in Human Esophageal Adenocarcinoma Cells

被引:28
作者
Delgado, Jorge-Shmuel [1 ]
Mustafi, Reba [1 ]
Yee, Jason [2 ]
Cerda, Sonia [1 ]
Chumsangsri, Anusara [1 ]
Dougherty, Urszula [1 ]
Lichtenstein, Lev [1 ]
Fichera, Alessandro [3 ]
Bissonnette, Marc [1 ]
机构
[1] Univ Chicago, Dept Med, Gastroenterol Sect, Med Ctr, Chicago, IL 60637 USA
[2] Univ Chicago, Div Social Sci, Inst Mind & Biol, Chicago, IL 60637 USA
[3] Univ Chicago, Med Ctr, Dept Surg, Chicago, IL 60637 USA
关键词
Sorafenib; Cyclin D1; Cyclin E; Barrett's esophagus; Esophageal adenocarcinoma;
D O I
10.1007/s10620-008-0294-y
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:3055 / 3064
页数:10
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