Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
National Center of Colorectal Surgery, Jiangsu Integrate Colorectal Oncology Center, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, PR China.
Eur J Pharmacol. 2019 Sep 15;859:172525. doi: 10.1016/j.ejphar.2019.172525. Epub 2019 Jul 6.
Emodin can effectively inhibit colorectal cancer cells, but the mechanism remains elusive. This study analyzed the changes of VEGFR2 signaling pathways in patients with colorectal cancer and the effects of emodin on HCT116 cells and xenograft tumor model. The expression levels of VEGFR2, PI3K, and p-AKT in colorectal cancer tissue samples were significantly higher than those in adjacent normal ones. Docking simulation confirmed that emodin bound the hydrophobic pocket and partially overlapped with the binding sites of VEGFR2, thus disrupting VEGFR2 dimerization. Western blotting further confirmed that emodin significantly inhibited the expression of VEGFR2, and reduced the expressions of PI3K and p-AKT in HCT116 cells. Furthermore, it suppressed the growth, adhesion and migration of HCT116 cells. In addition, emodin inhibited the tumor growth in xenograft model and the expressions of VEGFR2, PI3K and p-AKT in vivo. In conclusion, emodin suppressed the growth of colorectal cancer cells by inhibiting VEGFR2, as a potential candidate for therapy.
大黄素能有效抑制结直肠癌细胞，但作用机制尚不清楚。本研究分析了结直肠癌患者 VEGFR2 信号通路的变化以及大黄素对 HCT116 细胞和异种移植肿瘤模型的影响。结直肠癌组织样本中 VEGFR2、PI3K 和 p-AKT 的表达水平明显高于相邻正常组织。对接模拟证实，大黄素结合疏水口袋，与 VEGFR2 的结合位点部分重叠，从而破坏 VEGFR2 二聚化。Western blot 进一步证实，大黄素显著抑制 VEGFR2 的表达，并降低 HCT116 细胞中 PI3K 和 p-AKT 的表达。此外，它还抑制了 HCT116 细胞的生长、黏附和迁移。此外，大黄素抑制了异种移植模型中的肿瘤生长以及体内 VEGFR2、PI3K 和 p-AKT 的表达。总之，大黄素通过抑制 VEGFR2 抑制结直肠癌细胞的生长，有望成为一种治疗方法。
