Phytosomal curcumin inhibits tumor growth in colitis-associated colorectal cancer
Phytosomal curcumin inhibits tumor growth in colitis-associated colorectal cancer
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DOI：
10.1002/jcp.26538
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发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Khazaei, Majid
中科院分区：
文献类型：
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作者：
Marjaneh, Reyhaneh Moradi;Rahmani, Farzad;Khazaei, Majid
结直肠癌(CRC)是导致癌症死亡的第三大原因，需要寻找新的抗癌药物来提高现有治疗方法的疗效。有越来越多的数据显示姜黄素的抗肿瘤活性，尽管它与低吸收有关。本研究的目的是探讨新型植体姜黄素的治疗潜力及其与5-氟尿嘧啶(5-FU)联合应用于结肠炎相关性结肠癌的小鼠模型。在二维和三维细胞培养模型以及结肠炎相关结肠癌的小鼠模型中，对植体姜黄素的抗增殖活性进行了评估。用qRT-PCR和/或Western-blotting检测细胞周期蛋白D1、Beclin、E-钙粘蛋白和p-GSK3a/b的表达水平。通过病理评价和疾病活动性指数(DAI)评价该制剂的抗炎作用。用丙二醛(MDA)、总硫醇(T-SH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性参数检测氧化/抗氧化活性。我们的研究结果表明，植体姜黄素及其与5-FU联合应用可通过调节Wnt途径和E-钙粘附素抑制大肠癌细胞的生长和侵袭行为。姜黄素联合5-FU可显著减少结肠炎相关性结肠癌远端和中段的肿瘤数目和肿瘤大小，并降低DAI。姜黄素还能抑制大鼠结肠炎症反应，显著恢复升高的丙二醛水平、降低硫醇水平和降低过氧化氢酶活性。我们证明了新型姜黄素在结直肠癌中的抗肿瘤活性，支持进一步研究这种方法在结直肠癌中的治疗潜力。
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.