Ilhan Nevin, Gungor Hilal, Gul H Fatih, Eroksuz Hatice
Department of Medical Biochemistry, Firat University Faculty of Veterinary Medicine, Elazig, Turkey
Department of Medical Biochemistry, Firat University Faculty of Veterinary Medicine, Elazig, Turkey.
Anticancer Res. 2016 Aug;36(8):3953-9.
BACKGROUND/AIM: Endoglin (CD105) is a receptor for the transforming growth factor-beta 1 (TGFβ1) with crucial role in vascular development and angiogenesis. Additionally, vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival for several cancer types. These molecules have been shown to be useful markers for identifying proliferating endothelium involved in tumor angiogenesis, especially in patients with cancer at risk of developing metastases. The aim of this study was to evaluate the relationship between VEGF and endoglin expression in an experimental model of colorectal cancer, as well as to investigate the effect of cyclooxygenase-2 (COX2) inhibitors on tumor development incidence.
Colon cancer was induced with 1,2-dimethylhydrazine dihydrochloride (DMH). Celecoxib and diclofenac treatment was started simultaneously with DMH induction. Endoglin protein expression was performed using western blot analysis. VEGF plasma concentrations were measured by enzyme-linked immunosorbent assay.
In histopathological evaluations, no pathological change was observed in control rats, while adenocarcinoma (62.5%), dysplasia (31.25%) and inflammation (6.25%) were detected in the group given DMH. In treatment groups, a marked decrease was observed in adenocarcinoma rate. Expression of endoglin protein was significantly elevated in the DMH group compared to controls (p<0.001). No statistically significant difference was noted between treatment groups and DMH group regarding endoglin expression but a decrease was detected in the celecoxib-treated groups.
It was confirmed by histopathology and western blotting that COX2 inhibitors, particularly celecoxib, decrease the rate of disease and slow-down progression of existing CRC. These data show that endoglin expression may have an important role in tumor angiogenesis and predict of tumor invasion.
背景/目的：内皮糖蛋白（CD105）是转化生长因子-β1（TGFβ1）的受体，在血管发育和血管生成中起关键作用。此外，血管内皮生长因子（VEGF）的过表达与几种癌症类型的晚期阶段和不良生存率相关。这些分子已被证明是识别参与肿瘤血管生成的增殖内皮的有用标志物，特别是在有发生转移风险的癌症患者中。本研究的目的是评估结直肠癌实验模型中VEGF与内皮糖蛋白表达之间的关系，并研究环氧合酶-2（COX2）抑制剂对肿瘤发生发生率的影响。
用二盐酸1,2-二甲基肼（DMH）诱导结肠癌。塞来昔布和双氯芬酸治疗与DMH诱导同时开始。使用蛋白质免疫印迹分析进行内皮糖蛋白的蛋白表达检测。通过酶联免疫吸附测定法测量VEGF血浆浓度。
在组织病理学评估中，对照组大鼠未观察到病理变化，而给予DMH的组中检测到腺癌（62.5%）、发育异常（31.25%）和炎症（6.25%）。在治疗组中，腺癌发生率显著降低。与对照组相比，DMH组中内皮糖蛋白的蛋白表达显著升高（p<0.001）。治疗组和DMH组在内皮糖蛋白表达方面未观察到统计学上的显著差异，但在塞来昔布治疗组中检测到表达降低。
组织病理学和蛋白质免疫印迹证实，COX2抑制剂，特别是塞来昔布，可降低疾病发生率并减缓现有结直肠癌的进展。这些数据表明，内皮糖蛋白表达可能在肿瘤血管生成和肿瘤侵袭预测中起重要作用。
