Emodin suppresses growth and invasion of colorectal cancer cells by inhibiting VEGFR2
| Autor: | Guoliang Dai, Qianyu Cao, Fan He, Wenzheng Ju, Kang Ding, Shijia Liu, Tian Xu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Emodin Colorectal cancer Protein Conformation Antineoplastic Agents 03 medical and health sciences chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine In vivo Cell Movement medicine Cell Adhesion Animals Humans Neoplasm Invasiveness PI3K/AKT/mTOR pathway Cell Proliferation Pharmacology Chemistry respiratory system medicine.disease HCT116 Cells Vascular Endothelial Growth Factor Receptor-2 Xenograft Model Antitumor Assays Blot Molecular Docking Simulation 030104 developmental biology Cell culture Apoptosis cardiovascular system Cancer research Signal transduction Colorectal Neoplasms Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery circulatory and respiratory physiology Signal Transduction |
| Zdroj: | European journal of pharmacology. 859 |
| ISSN: | 1879-0712 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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