Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Physiol. 2018 Oct;233(10):6785-6798. doi: 10.1002/jcp.26538. Epub 2018 May 8.
Colorectal-cancer (CRC) is the third leading cause of death due to cancer, supporting the need for identification of novel anticancer drug to improve the efficacy of current-therapy. There is growing bodies of data showing the antitumor-activity of curcumin, although it is associated with low absorption. The aim of current study was explored the therapeutic-potential of novel phytosomal curcumin as well as its application in combination with 5-Flurouracil (5-FU) in a mouse-model of colitis-associated colon-cancer. The anti-proliferative-activity of phytosomal curcumin was assessed in 2- and 3-dimensional cell-culture-models as well as in a mouse-model of colitis-associated colon-cancer. The expression-levels of CyclinD1, beclin, E-cadherin, and p-GSK3a/b were investigated by qRT-PCR and/or Western-blotting. We evaluated the anti-inflammatory of this agent by pathological-evaluation and disease-activity-index (DAI). Moreover, oxidant/antioxidant activity was examined by malondialdehyde (MDA), total-thiols (T-SH), superoxide-dismutase (SOD), and catalase (CAT) activity parameters. Our data showed that phytosomal curcumin and its combination with 5-FU inhibited cell growth and invasive behavior of CRC cells through modulation of Wnt-pathway and E-cadherin. Combination of curcumin with 5-FU dramatically reduced the tumor-number and tumor-size in both distal and middle parts of colon in colitis-associated colon cancer followed by reduction in DAI. Also, curcumin suppressed the colonic inflammation and notably recovered the increased levels of MDA, decreased thiol level and reduced activity of CAT. We demonstrated the antitumor-activity of novel form of curcumin in CRC, supporting further investigations on the therapeutic-potential of this approach in colorectal-cancer.
结直肠癌（CRC）是癌症导致死亡的第三大主要原因，这支持了需要寻找新的抗癌药物以提高当前疗法的疗效的观点。越来越多的数据表明姜黄素具有抗肿瘤活性，尽管它的吸收率较低。目前的研究旨在探索新型姜黄素质体的治疗潜力及其与 5-氟尿嘧啶（5-FU）联合应用于结肠炎相关结肠癌小鼠模型中的效果。通过 2 维和 3 维细胞培养模型以及结肠炎相关结肠癌小鼠模型评估了姜黄素质体的抗增殖活性。通过 qRT-PCR 和/或 Western blot 检测细胞周期蛋白 D1、beclin、E-钙粘蛋白和 p-GSK3a/b 的表达水平。通过病理评估和疾病活动指数（DAI）评估该药物的抗炎作用。此外，通过丙二醛（MDA）、总巯基（T-SH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性参数评估氧化应激/抗氧化活性。我们的数据表明，姜黄素质体及其与 5-FU 的联合应用通过调节 Wnt 通路和 E-钙粘蛋白抑制 CRC 细胞的生长和侵袭行为。姜黄素与 5-FU 的联合应用显著减少了结肠炎相关结肠癌远端和中段的肿瘤数量和肿瘤大小，随后 DAI 降低。此外，姜黄素抑制了结肠炎症，并显著恢复了 MDA 水平的升高、硫醇水平的降低和 CAT 活性的降低。我们证明了新型姜黄素在 CRC 中的抗肿瘤活性，支持进一步研究这种方法在结直肠癌中的治疗潜力。
