RRC ID |
44134
|
著者 |
Miyamoto C, Maehata Y, Ozawa S, Ikoma T, Kubota E, Izukuri K, Kato Y, Hata R, Lee MC.
|
タイトル |
Fasudil suppresses fibrosarcoma growth by stimulating secretion of the chemokine CXCL14/BRAK.
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ジャーナル |
J Pharmacol Sci
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Abstract |
We previously reported that chemokine CXCL14/BRAK (BRAK) has antitumor activity in several carcinoma cells indicating that BRAK secretion suppresses carcinoma cells. Ras-homologous small GTPase (RhoA) and Rho-associated coiled-coil-containing protein kinase (ROCK) are important regulators of secretory processes, and activation of the RhoA/ROCK signaling pathway stimulates tumor invasion and metastasis. We investigated the effects of fasudil, a specific ROCK inhibitor, on BRAK secretion and tumor progression in mesenchymal fibrosarcoma cells (MC57). We demonstrated the antitumor activity of secreted BRAK using MC57 transplantation of BRAK in overexpressed transgenic mice. Further, to eliminate the influence of change in the mRNA expression of endogenous BRAK, we produced stable MC57 cell lines expressing BRAK (MC57-BRAK) or mock vector (MC57-MOCK). Fasudil significantly increased BRAK secretion by MC57-BRAK cells in a dose-dependent manner. To determine the effect of fasudil on tumor growth, MC57-BRAK and MC57-MOCK cells were transplanted into wild-type mice. Fasudil treatment suppressed tumor growth only in mice that had received MC57-BRAK cell transplants. These results indicate that fasudil inhibits fibrosarcoma growth by stimulating BRAK secretion and suggests that fasudil therapy might have clinical efficacy.
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巻・号 |
120(3)
|
ページ |
241-9
|
公開日 |
2012-1-1
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DOI |
10.1254/jphs.12177fp
|
PII |
DN/JST.JSTAGE/jphs/12177FP
|
PMID |
23099322
|
MeSH |
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Cell Proliferation / drug effects
Chemokines, CXC / genetics
Chemokines, CXC / metabolism*
Fibrosarcoma / drug therapy*
Fibrosarcoma / metabolism
Fibrosarcoma / pathology
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Neoplasm Transplantation
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use*
Recombinant Proteins / metabolism
Signal Transduction / drug effects
Tumor Burden / drug effects
Up-Regulation / drug effects
rho-Associated Kinases / antagonists & inhibitors*
rhoA GTP-Binding Protein / metabolism
|
IF |
2.835
|
引用数 |
11
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
|