Department of Otolaryngology, Head and Neck Surgery, Universitaets-HNO-Klinik, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany.
Anticancer Res. 2010 Feb;30(2):339-43.
The most common neoplasm arising in the upper gastrointestinal tract is head and neck squamous cell carcinoma (HNSCC). This is an aggressive epithelial malignancy. Many growth factors and cytokines have been discovered that are responsible for the growth and formation of tumours. Among these factors, beta-catenin is considered to be the most important for reducing cell-cell adhesions in malignant tissue. The degradation of beta-catenin triggers apoptosis by different routes. Sulindac sulfone has been shown to induce apoptosis in several different tumours. In the present study, we surveyed the concentration of beta-catenin in an HNSCC line after incubation with different concentrations of sulindac sulfone.
Immunohistochemical and Western blot analyses were performed after treatment of the UMSCC 11A cell line with different concentrations of sulindac sulfone (100, 200, 400, 600 and 800 microMol) for 48 hours.
At 100 microMol of sulindac sulfone, a decrease in beta-catenin concentration of 5% was observed; increasing concentrations of sulindac sulfone resulted in >70% reduction in secreted beta-catenin. Thus in conclusion, incubation with sulindac sulfone seemed to stop proliferation. With respect to the controls, there was no greater reduction in total protein.
In this study, sulindac sulfone reduced levels of secreted beta-catenin in the HNSCC cell line UM-SCC 11A after 48 hours of incubation. It is presumed that reduction of cell-cell adhesion, which is predominately affected by beta-catenin, is an essential step in the progression from localized malignancy to stromal and vascular invasion and ultimately metastatic disease. The reduction in the level of mural expression of beta-catenin has been associated with loss of differentiation in laryngeal carcinomas. Thus, prevention of intracellular beta-catenin accumulation is regarded as an attractive target for chemopreventive agents.
上消化道最常见的肿瘤是头颈部鳞状细胞癌（HNSCC）。这是一种侵袭性上皮恶性肿瘤。已经发现许多生长因子和细胞因子负责肿瘤的生长和形成。在这些因子中，β-连环蛋白被认为是降低恶性组织中细胞间黏附的最重要因子。β-连环蛋白的降解通过不同途径触发细胞凋亡。已表明舒林酸砜可诱导几种不同肿瘤的细胞凋亡。在本研究中，我们调查了不同浓度舒林酸砜孵育后 HNSCC 细胞系中β-连环蛋白的浓度。
用不同浓度的舒林酸砜（100、200、400、600 和 800 μmol）处理 UMSCC 11A 细胞系 48 小时后，进行免疫组织化学和 Western blot 分析。
在 100 μmol 的舒林酸砜下，β-连环蛋白浓度降低了 5%；随着舒林酸砜浓度的增加，分泌的β-连环蛋白减少了>70%。因此，总之，孵育舒林酸砜似乎停止了增殖。与对照组相比，总蛋白没有更大的减少。
在这项研究中，舒林酸砜在孵育 48 小时后降低了 HNSCC 细胞系 UM-SCC 11A 中分泌的β-连环蛋白水平。据推测，细胞间黏附的减少，主要受β-连环蛋白的影响，是从局部恶性肿瘤向基质和血管浸润以及最终转移疾病进展的关键步骤。β-连环蛋白壁表达水平的降低与喉癌分化丧失有关。因此，预防细胞内β-连环蛋白的积累被认为是化学预防剂的一个有吸引力的靶标。
