Inhibitory effects of tanshinone II-A on invasion and metastasis of human colon carcinoma cells.
OBJECTIVE
To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.


METHODS
The effects of tanshinone II-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone II-A anti-cancer actions.


RESULTS
Tanshinone II-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone II-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-kappaB) signal.


CONCLUSIONS
Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1 and TIMP-2, and apparent inhibition of the NF-kappaB signal transduction pathway.
Shan
Yun-feng
YF
Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
Shen
Xian
X
Xie
Yuan-kang
YK
Chen
Ji-cai
JC
Shi
Hong-qi
HQ
Yu
Zheng-ping
ZP
Song
Qi-tong
QT
Zhou
Men-tao
MT
Zhang
Qi-yu
QY
D045784:Abietanes; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010616:Phenanthrenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018517:Plant Roots; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; D010936:Plant Extracts; C021751:tanshinone