Delgado Jorge-Shmuel, Mustafi Reba, Yee Jason, Cerda Sonia, Chumsangsri Anusara, Dougherty Urszula, Lichtenstein Lev, Fichera Alessandro, Bissonnette Marc
Section of Gastroenterology, Department of Medicine, The University of Chicago Medical Center, MC 4076. 5841 S. Maryland Ave, Chicago, IL, 60637, USA.
Dig Dis Sci. 2008 Dec;53(12):3055-64. doi: 10.1007/s10620-008-0294-y. Epub 2008 May 30.
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.
目前的治疗方法对晚期食管腺癌患者益处甚微。我们研究了多激酶抑制剂索拉非尼对源自巴雷特腺癌的SEG-1细胞中几种控制细胞生长和存活的生长调节通路的影响。
将SEG-1细胞暴露于酸化培养基或牛磺胆酸中，且有无索拉非尼预孵育。通过蛋白质印迹法测定细胞周期蛋白D1和E、c-Myc以及Bcl-2的表达水平以及信号转导和转录激活因子3（STAT3）的激活情况。通过实时聚合酶链反应（PCR）测量细胞周期蛋白D1信使核糖核酸（mRNA）。通过末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）检测细胞凋亡。
索拉非尼显著抑制酸或胆汁酸处理刺激的SEG-1细胞增殖并降低细胞存活率。该药物显著降低SEG-1细胞中细胞周期蛋白D1、细胞周期蛋白E、c-Myc和Bcl-2的上调以及STAT3的激活。
这些结果为未来评估索拉非尼在食管腺癌治疗中的益处的临床研究提供了合理依据。
