Danthron inhibits the migration and invasion of human brain glioblastoma multiforme cells through the inhibition of mRNA expression of focal adhesion kinase, Rho kinases-1 and metalloproteinase-9.
In this study, we investigated the effect of danthron on the cell migration and invasion of human brain glioblastoma multiforme GBM 8401 cells in vitro. The changes of migration and invasion of GBM 8401 cells after treatment with danthron were detected by cell migration assay and cell invasion assay. The levels of mRNA gene expression associated with cell migration and invasion were detected by real-time PCR. Results indicated that human brain glioblastoma multiforme GBM 8401 cells treated with danthron in vitro migrated and invaded less than cells treated with phosphate-buffered saline (PBS) (control). Western blotting showed that danthron inhibited the protein levels of FAK, MMP-7, MMP-9 and uPA in GBM 8401 cells. Real-time PCR assay also showed that danthron inhibited the mRNA expression of matrix metalloproteinase-9 (MMP-9), FAK and ROCK-1 of GBM 8401 cells. These results showed that danthron inhibited invasion and migration of GBM 8401 cells by downregulating mRNA expression associated with these processes, resulting in reduced metastasis. Thus, danthron may be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.
Lin
Chin-Chung
CC
Fong-Yuan Hospital, Department of Health, Executive Yuan, Fong Yuan 402, Taiwan, ROC.
Chen
Jin-Tang
JT
Yang
Jai-Sing
JS
Lu
Hsu-Feng
HF
Hsu
Shu-Chun
SC
Tan
Tzu-Wei
TW
Lin
Yuh-Tzy
YT
Ma
Yi-Shih
YS
Ip
Siu-Wan
SW
Wu
Jia-Jiuan
JJ
Li
Yu-Chinh
YC
Chung
Jing-Gung
JG
D000880:Anthraquinones / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
D000880:Anthraquinones; D009153:Mutagens; D012333:RNA, Messenger; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D054460:rho-Associated Kinases; D020780:Matrix Metalloproteinase 9; C004315:danthron