Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Biomed Pharmacother. 2017 Nov;95:387-393. doi: 10.1016/j.biopha.2017.08.103. Epub 2017 Sep 12.
In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12.5mg/kg, i.p.) or Ginkgo biloba L. leaf extract in a dose of 0.675 and 1.35g/kg, p.o. respectively. The developed tumor enhanced plasma TGF-β, and Bcl, serum EGF, CEA, CCSA, and MMP-7 significantly. Also, gene expression analysis showed significant upregulation of colonic β-Catenin, K-ras and C-myc genes. Besides, immunohistochemical findings revealed significant increase in COX-2, cyclin D1 and survivin content in colon tissue. These data were further supported by the histological observations. Ginkgo biloba L. leaf extract-treated rats; particularly those treated with dose of 1.35g/kg, exhibited significant reduction in the aforementioned parameters and improvement in the histological organization of the colon tissue. The therapeutic effect of Ginkgo biloba L. leaf extract was comparable with that mediated by 5-FU. The current research proved that Ginkgo biloba L. leaf extract could suppress tumor cell proliferation, promote apoptosis, and mitigat inflammation in vivo. The amelioration of these key events might be linked with the inhibition of Wnt/β-Catenin signaling module. The outcomes of the present investigation encourage the use of Ginkgo biloba L. leaf extract as a complementary and alternative therapeutic approach to abate CRC.
在埃及，结直肠癌（CRC）在两性中均排名第 6，并且 40 岁以下人群的 CRC 发病率较高。本研究旨在使用相关的生化标志物来确定 CRC 的发展，并阐明银杏叶提取物在实验性 CRC 逆转中的潜在机制。成年雄性 Sprague-Dawley 大鼠每周三次通过直肠内给予 N-甲基-N-亚硝脲（N-MNU；2mg 溶于 0.5ml 水中/只），共 5 周，以诱导 CRC，然后分别用 5-氟尿嘧啶（5-FU；12.5mg/kg，腹腔内注射）或银杏叶提取物以 0.675 和 1.35g/kg 的剂量进行治疗，口服。发展中的肿瘤显著增加了血浆 TGF-β 和 Bcl，血清 EGF、CEA、CCSA 和 MMP-7。此外，基因表达分析显示结肠 β-连环蛋白、K-ras 和 C-myc 基因的表达显著上调。此外，免疫组织化学发现结肠组织中 COX-2、cyclin D1 和 survivin 含量显著增加。这些数据得到了组织学观察的进一步支持。银杏叶提取物治疗的大鼠，特别是用 1.35g/kg 剂量治疗的大鼠，上述参数显著降低，结肠组织的组织学结构得到改善。银杏叶提取物的治疗效果可与 5-FU 介导的效果相媲美。目前的研究证明，银杏叶提取物可以抑制肿瘤细胞增殖，促进细胞凋亡，并在体内减轻炎症。这些关键事件的改善可能与 Wnt/β-连环蛋白信号模块的抑制有关。本研究的结果鼓励使用银杏叶提取物作为一种补充和替代治疗方法来减轻 CRC。
