Silibinin inhibits invasion of oral cancer cells by suppressing the MAPK pathway

被引:94
作者
Chen, PN
Hsieh, YS
Chiang, CL
Chou, HL
Yang, SF
Chu, SC
机构
[1] Chung Shan Med Univ, Inst Biochem, Taichung 402, Taiwan
[2] Chung Shan Med Univ, Sch Med Technol, Taichung 402, Taiwan
[3] Cent Taiwan Univ Sci & Technol, Dept Food Sci, Taichung 406, Taiwan
关键词
silibinin; invasion; MMP-2; u-PA;
D O I
10.1177/154405910608500303
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Here, we provide molecular evidence associated with the anti-metastatic effect of silibinin by showing a marked inhibition of the invasion and motility of SCC-4 tongue cancer cells, with 89% and 66.4% of inhibition, respectively, by 100 mu M of silibinin. This effect was associated with a reduced expression of MMP-2 and u-PA, together with an enhanced expression of TIMP-2 and PAI-1. Silibinin also exerted an inhibitory effect on the phosphorylation of ERK1/2. Additionally, pretreatment of SCC-4 cancer cells with 10 and 20 mu M of U0126, a specific MEK inhibitor, resulted in a reduced expression of MMP-2 (18.7 and 51.4%) and u-PA (19.2 and 48.9%) concomitantly with a marked inhibition of cell invasion (13.7 and 45.7%). Finally, silibinin was evidenced by its inhibition of the metastasis of Lewis lung carcinoma (LLC) cells in vivo. These results suggested that silibinin can reduce the invasion and metastasis of tumor cells, and such a characteristic may be of great value in the development of a potential cancer therapy.
引用
收藏
页码:220 / 225
页数:6
相关论文
共 28 条
[1]   Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells [J].
Agarwal, C ;
Singh, RP ;
Dhanalakshmi, S ;
Tyagi, AK ;
Tecklenburg, M ;
Sclafani, RA ;
Agarwal, R .
ONCOGENE, 2003, 22 (51) :8271-8282
[2]   INHIBITORY EFFECT OF SILYMARIN, AN ANTIHEPATOTOXIC FLAVONOID, ORE 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED EPIDERMAL ORNITHINE DECARBOXYLASE ACTIVITY AND MESSENGER-RNA IN SENCAR MICE [J].
AGARWAL, R ;
KATIYAR, SK ;
LUNDGREN, DW ;
MUKHTAR, H .
CARCINOGENESIS, 1994, 15 (06) :1099-1103
[3]  
AZZAM HS, 1992, CANCER RES, V52, P4540
[4]   Oral cavity and pharynx cancer incidence rates in the United States, 1975-1998 [J].
Canto, MT ;
Devesa, SS .
ORAL ONCOLOGY, 2002, 38 (06) :610-617
[5]  
CHEN PN, 2006, IN PRESS CANC LETT
[6]   Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and Matrix metalloproteinase-2 [J].
Chu, SC ;
Chiu, HL ;
Chen, PN ;
Yang, SF ;
Hsieh, YS .
MOLECULAR CARCINOGENESIS, 2004, 40 (03) :143-149
[7]  
Geletu Gabriela, 2004, Rev Med Chir Soc Med Nat Iasi, V108, P79
[8]  
Kurahara S, 1999, HEAD NECK-J SCI SPEC, V21, P627, DOI 10.1002/(SICI)1097-0347(199910)21:7<627::AID-HED7>3.3.CO
[9]  
2-U
[10]   Suppression of distant pulmonary metastasis of MDA-MB 435 human breast carcinoma established in mammary fat pads of nude mice by retroviral-mediated TIMP-2 gene transfer [J].
Lee, YK ;
So, IS ;
Lee, SC ;
Lee, JH ;
Lee, CW ;
Kim, WM ;
Park, MK ;
Lee, ST ;
Park, DY ;
Shin, DY ;
Park, CU ;
Kim, YS .
JOURNAL OF GENE MEDICINE, 2005, 7 (02) :145-157