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.
ジャーナル J Pharmacol Sci
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.
巻・号 120(3)
ページ 241-9
公開日 2012-1-1
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