Coptisine suppresses tumor growth and progression by down-regulating MFG-E8 in colorectal cancer

被引:31
作者
Cao, Qianyu [1 ]
Hong, Shengwei [1 ]
Li, Yuanyuan [1 ]
Chen, Heng [1 ]
Shen, Yining [1 ]
Shao, Kang [1 ]
Lu, Mengjie [1 ]
Dai, Hui [1 ]
Ma, Shitang [2 ]
Dai, Guoliang [3 ]
机构
[1] Nanjing Univ Chinese Med, Clin Coll 1, Nanjing 210023, Jiangsu, Peoples R China
[2] Anhui Sci & Technol Univ, Coll Life & Hlth Sci, Fengyang 233100, Peoples R China
[3] Nanjing Univ Chinese Med, Affiliated Hosp, Dept Clin Pharmacol, Nanjing 210029, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
PI3K/AKT SIGNALING PATHWAY; ACTIVATION; ADHESION; CELLS;
D O I
10.1039/c8ra05806g
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Treating colorectal cancer (CRC) continues to be a clinical challenge. Coptisine, an alkaloid derived from Coptis chinensis Franch. shows toxic effects on CRC cells, but its underlying mechanism remains elusive. MFG-E8 is involved in tumor growth and progression. Herein, we evaluated the effects of coptisine on MFG-E8 in CRC, and explored the mechanism. The expression of MFG-E8 in CRC and adjacent normal colon tissue samples from patients was detected. The effects of coptisine on CRC cells HCT116 in vitro were evaluated by CCK-8, adhesion and transwell assays. A xenograft tumor model was used to assess the effects of coptisine in vivo. The morphology of CRC tissue was observed by HE staining. Cell signaling was tested using western blotting and immunohistochemical assay. The expression of MFG-E8 in human CRC tissue samples significantly increased compared with that of adjacent normal ones. Coptisine significantly reduced the expressions of MFG-E8 in HCT116 cells and tumor-bearing mice. Moreover, coptisine suppressed the growth, adhesion and metastasis of CRC cells. Coptisine also suppressed the expression of MMP-2 and MMP-9 via the PI3K/AKT signaling pathway. Furthermore, it inhibited epithelial-mesenchymal transition in vivo and in vitro. Coptisine inhibited CRC growth and progression by down-regulating MFG-E8, and is a potential candidate for treatment.
引用
收藏
页码:30937 / 30945
页数:9
相关论文
共 23 条
[1]   αVβ3 Integrin Regulates Macrophage Inflammatory Responses via PI3 Kinase/Akt-Dependent NF-κB Activation [J].
Antonov, Alexander S. ;
Antonova, Galina N. ;
Munn, David H. ;
Mivechi, Nahid ;
Lucas, Rudolf ;
Catravas, John D. ;
Verin, Alexander D. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (02) :469-476
[2]   Prognostic and diagnostic implications of MMP-2, MMP-9, and VEGF-α expressions in colorectal cancer [J].
Araujo, R. F., Jr. ;
Lira, G. A. ;
Vilaca, J. A. ;
Guedes, H. G. ;
Leitao, M. C. A. ;
Lucena, H. F. ;
Ramos, C. C. O. .
PATHOLOGY RESEARCH AND PRACTICE, 2015, 211 (01) :71-77
[3]   Colorectal cancer [J].
Cunningham, David ;
Atkin, Wendy ;
Lenz, Heinz-Josef ;
Lynch, Henry T. ;
Minsky, Bruce ;
Nordlinger, Bernard ;
Starling, Naureen .
LANCET, 2010, 375 (9719) :1030-1047
[4]   Portrait of the PI3K/AKT pathway in colorectal cancer [J].
Danielsen, Stine Aske ;
Eide, Peter Wold ;
Nesbakken, Arild ;
Guren, Tormod ;
Leithe, Edward ;
Lothe, Ragnhild A. .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2015, 1855 (01) :104-121
[5]   Genetics, diagnosis and management of colorectal cancer [J].
De Rosa, Marina ;
Pace, Ugo ;
Rega, Daniela ;
Costabile, Valeria ;
Duraturo, Francesca ;
Izzo, Paola ;
Delrio, Paolo .
ONCOLOGY REPORTS, 2015, 34 (03) :1087-1096
[6]   Activation of G protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals [J].
Guan, Bao-zhang ;
Yan, Rui-ling ;
Huang, Jian-Wei ;
Li, Fo-Lan ;
Zhong, Ying-Xue ;
Chen, Yu ;
Liu, Fan-Na ;
Hu, Bo ;
Huang, Si-Bo ;
Yin, Liang-Hong .
CELL ADHESION & MIGRATION, 2018, 12 (02) :109-117
[7]   Coptisine from Rhizoma Coptidis Suppresses HCT-116 Cells-related Tumor Growth in vitro and in vivo [J].
Huang, Tao ;
Xiao, Yubo ;
Yi, Lin ;
Li, Ling ;
Wang, Meimei ;
Tian, Cheng ;
Ma, Hang ;
He, Kai ;
Wang, Yue ;
Han, Bing ;
Ye, Xiaoli ;
Li, Xuegang .
SCIENTIFIC REPORTS, 2017, 7
[8]   Prognostic Correlation Between MFG-E8 Expression Level and Colorectal Cancer [J].
Jia, Min ;
Yao, Huaning ;
Chen, Chao ;
Wang, Yueqin ;
Wang, Han ;
Cui, Tianpen ;
Zhu, Jianhua .
ARCHIVES OF MEDICAL RESEARCH, 2017, 48 (03) :270-275
[9]   Milk Fat Globule EGF-8 Promotes Melanoma Progression through Coordinated Akt and Twist Signaling in the Tumor Microenvironment [J].
Jinushi, Masahisa ;
Nakazaki, Yukoh ;
Carrasco, Daniel R. ;
Draganov, Dobrin ;
Souders, Nicholas ;
Johnson, Matthew ;
Mihm, Martin C. ;
Dranoff, Glenn .
CANCER RESEARCH, 2008, 68 (21) :8889-8898
[10]   Protein quantification and its tolerance for different interfering reagents using the BCA-method with regard to 2D SDS PAGE [J].
Krieg, RC ;
Dong, Y ;
Schwamborn, K ;
Knuechel, R .
JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, 2005, 65 (01) :13-19