Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway

被引:24
作者
Liu, Ji Ping [1 ,2 ]
Liu, Dan [1 ]
Gu, Jun Fei [1 ]
Zhu, Mao Mao [1 ]
Cui, Li [1 ]
机构
[1] Jiangsu Prov Acad Chinese Med, Key Lab New Drug Delivery Syst Chinese Mat Med, Nanjing 210028, Jiangsu, Peoples R China
[2] Shaanxi Univ Chinese Med, Dept Pharmacol, Xianyang, Peoples R China
关键词
gastric cancer; invasion; migratory; Shikonin; toll-like receptor-2; MATRIX METALLOPROTEINASES; HEPATOCELLULAR-CARCINOMA; MMP-9; EXPRESSION; METASTASIS; APOPTOSIS; PROMOTES; OSTEOSARCOMA; SUPPRESSES; INDUCTION; GROWTH;
D O I
10.1111/jphp.12402
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ObjectivesShikonin is an active naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon. This study was designed to explore the inhibition of Shikonin on cell viability, adhesion, migration and invasion ability of gastric cancer (GC) and its possible mechanism. Methods3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for cell viability and adhesion ability of MGC-803 cells. Cell scratch repair experiments were conducted for the determination of migration ability while transwell assay for cell invasion ability. Western blot analysis and real-time polymerase chain reaction assay were used for the detection of protein and mRNA expressions. Key findingsFifty per cent inhibitory concentration of Shikonin on MGC-803 cells was 1.854m. Shikonin (1m) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells. Interestingly, Shikonin in the presence or absence of anti-Toll-like receptor 2 (TLR2) antibody (2g) and nuclear factor-kappa B (NF-B) inhibitor MG-132 (10m) could decrease these ability of MGC-803 cells markedly, as well as the expression levels of matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-B. In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone. ConclusionsThe results indicated that Shikonin could suppress the cell viability, adhesion, invasion and migratory ability of MGC-803 cells through TLR2- or NF-B-mediated pathway. Our findings provide novel information for the treatment of Shikonin on GC.
引用
收藏
页码:1143 / 1155
页数:13
相关论文
共 40 条
[1]   Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer [J].
Banyard, Jacqueline ;
Chung, Ivy ;
Migliozzi, Matthew ;
Phan, Derek T. ;
Wilson, Arianne M. ;
Zetter, Bruce R. ;
Bielenberg, Diane R. .
BMC CANCER, 2014, 14
[2]   Shikonin Induces Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase Pathway in Osteosarcoma Cells [J].
Chang, I-Chang ;
Huang, Yu-Jen ;
Chiang, Tsay-I ;
Yeh, Chi-Wei ;
Hsu, Li-Sung .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2010, 33 (05) :816-824
[3]   Shikonin, a natural product from the root of Lithospermum erythrorhizon, is a cytotoxic DNA-binding agent [J].
Chen, Changmin ;
Shanmugasundaram, Kumaran ;
Rigby, Alan C. ;
Kung, Andrew L. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2013, 49 (01) :18-26
[4]   Preface [J].
Chen, Hong ;
Brash, John .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2014, 124 :1-1
[5]   Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway [J].
Cheng, Xudong ;
Gu, Junfei ;
Zhang, Minghua ;
Yuan, Jiarui ;
Zhao, Bingjie ;
Jiang, Jun ;
Jia, Xiaobin .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2014, 23 (01) :304-313
[6]   Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer [J].
de Oliveira, Juliana Garcia ;
Teixeira Rossi, Ana Flavia ;
Nizato, Daniela Manchini ;
Miyasaki, Kenji ;
Silva, Ana Elizabete .
DIGESTIVE DISEASES AND SCIENCES, 2013, 58 (04) :978-988
[7]   Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population [J].
de Oliveira, Juliana Garcia ;
Silva, Ana Elizabete .
WORLD JOURNAL OF GASTROENTEROLOGY, 2012, 18 (11) :1235-1242
[8]   Factors correlated with peritoneal carcinomatosis and survival in patients with gastric cancer treated at a single institution in Brazil [J].
Fanelli, Marcello F. ;
Silva, Milton J. B. ;
de Paiva, Tadeu F., Jr. ;
Chinen, Ludmilla T. D. ;
Guimaraes, Andrea P. G. ;
Gimenes, Daniel L. ;
Pinheiro, Edilson D. ;
Rinck, Jose A., Jr. ;
Nicolau, Ulisses R. ;
Sanches, Solange M. ;
Melo, Celso A. L. ;
Dettino, Aldo L. A. ;
Cruz, Marcelo R. S. ;
de Melo, Leila Maria M. P. ;
Formiga, Maria N. C. ;
de Lima, Vladmir C. C. .
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 2009, 14 (04) :326-331
[9]   The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis [J].
Fu, Zeze ;
Deng, Biyong ;
Liao, Yuxin ;
Shan, Liancheng ;
Yin, Fei ;
Wang, Zhuoying ;
Zeng, Hui ;
Zuo, Dongqing ;
Hua, Yingqi ;
Cai, Zhengdong .
BMC CANCER, 2013, 13
[10]   Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma [J].
Gong, Ke ;
Li, Wenhua .
FREE RADICAL BIOLOGY AND MEDICINE, 2011, 51 (12) :2259-2271