Anti-metastatic activity of fangchinoline in human gastric cancer AGS cells

被引:20
作者
Chen, Zhengrong [1 ]
He, Tengfei [1 ]
Zhao, Kui [1 ]
Xing, Chungen [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Bldg 3,1055 Sanxiang Rd, Suzhou 215007, Jiangsu, Peoples R China
关键词
fangchinoline; gastric cancer; metastasis; MMPs; AKT; MATRIX METALLOPROTEINASES MMP-2; INVASION; EXPRESSION; ARREST;
D O I
10.3892/ol.2016.5457
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Fangchinoline (FCL) is an active component isolated from the traditional medicinal plant Stephania tetrandra S. Moore, and has been reported to possess anti-cancer functions in several types of cancers; however, the effect of FCL on gastric cancer metastasis and its underlying molecular mechanisms remain unknown. The current study aimed to investigate the effect of FCL on the cell migration and invasion of human metastatic gastric cancer AGS cells and its mechanisms. Our study demonstrates that FCL dosage dependently suppressed the adhesion, migration and invasion capacities of human gastric cancer AGS cells without obvious cytotoxic effects. Reverse transcription-polymerase chain reaction and western blot assays demonstrated that FCL greatly inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the mRNA and protein levels, while it significantly increased the expression of tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP2 messenger RNAs. Our results also indicated that FCL repressed the phosphorylation of AKT in gastric cancer AGS cells. In summary, FCL may exert its anti-metastatic property in human gastric cancer cells in vitro by suppression of MMP-2 and MMP-9, increase of TIMP1 and TIMP2 genes, and inhibition of AKT phosphorylation. FCL may be a drug candidate for the treatment of gastric cancer metastasis.
引用
收藏
页码:655 / 660
页数:6
相关论文
共 22 条
[1]   Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter [J].
Beliën, ATJ ;
Paganetti, PA ;
Schwab, ME .
JOURNAL OF CELL BIOLOGY, 1999, 144 (02) :373-384
[2]   Phenethyl isothiocyanate suppresses EGF-stimulated SAS human oral squamous carcinoma cell invasion by targeting EGF receptor signaling [J].
Chen, Hui-Jye ;
Lin, Chung-Ming ;
Lee, Chao-Ying ;
Shih, Nai-Chen ;
Amagaya, Sakae ;
Lin, Yung-Chang ;
Yang, Jai-Sing .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2013, 43 (02) :629-637
[3]   Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways [J].
Chen, PN ;
Hsieh, YS ;
Chiou, HL ;
Chu, SC .
CHEMICO-BIOLOGICAL INTERACTIONS, 2005, 156 (2-3) :141-150
[4]  
Deryugina EI, 1997, ANTICANCER RES, V17, P3201
[5]   Ethnobotany, phytochemistry and pharmacology of Stephania rotunda Lour [J].
Desgrouas, Camille ;
Taudon, Nicolas ;
Bun, Sok-Siya ;
Baghdikian, Beatrice ;
Bory, Sothavireak ;
Parzy, Daniel ;
Ollivier, Evelyne .
JOURNAL OF ETHNOPHARMACOLOGY, 2014, 154 (03) :537-563
[6]   Fangchinoline inhibited the antinociceptive effect of morphine in mice [J].
Fang, LH ;
Zhang, YH ;
Ku, BS .
PHYTOMEDICINE, 2005, 12 (03) :183-188
[7]   Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549 [J].
Guo, Bingyu ;
Su, Jingyuan ;
Zhang, Tingting ;
Wang, Kaiwen ;
Li, Xiaoming .
JOURNAL OF DRUG TARGETING, 2015, 23 (03) :266-274
[8]   Vasodilating and hypotensive effects of fangchinoline and tetrandrine on the rat aorta and the stroke-prone spontaneously hypertensive rat [J].
Kim, HS ;
Zhang, YH ;
Oh, KW ;
Ahn, HY .
JOURNAL OF ETHNOPHARMACOLOGY, 1997, 58 (02) :117-123
[9]   Fangchinoline inhibits glutamate release from rat cerebral cortex nerve terminals (synaptosomes) [J].
Lin, Tzu-Yu ;
Lu, Cheng-Wei ;
Tien, Lu-Tai ;
Chuang, Shu-Han ;
Wang, Yu-Ru ;
Chang, Wen-Hsuan ;
Wang, Su-Jane .
NEUROCHEMISTRY INTERNATIONAL, 2009, 54 (08) :506-512
[10]   Phyllanthus urinaria suppresses human osteosarcoma cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways [J].
Lu, Ko-Hsiu ;
Yang, Hui-Wen ;
Su, Chun-Wen ;
Lue, Ko-Huang ;
Yang, Shun-Fa ;
Hsieh, Yih-Shou .
FOOD AND CHEMICAL TOXICOLOGY, 2013, 52 :193-199