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   Fasudil suppresses fibrosarcoma growth by stimulating secretion of the chemokine CXCL14/BRAK  
   
نویسنده miyamoto c. ,maehata y. ,ozawa s. ,ikoma t. ,kubota e. ,izukuri k. ,kato y. ,hata r.-i. ,lee m.-c.-i.
منبع journal of pharmacological sciences - 2012 - دوره : 120 - شماره : 3 - صفحه:241 -249
چکیده    We previously reported that chemokine cxcl14/brak (brak) has antitumor activity in several carcinoma cells indicating that brak secretion suppresses carcinoma cells. rashomologous 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. © the japanese pharmacological society.
کلیدواژه 5-(1 ,4-Diazepane-1-sulfonyl) isoquinoline; CXCL14/BRAK; Fasudil; Fibrosarcoma cell; Ras-homologous small GTPase
آدرس department of clinical care medicine,division of pharmacology and esr laboratories,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of clinical care medicine,division of pharmacology and esr laboratories,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of oral surgery,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of oral surgery,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of oral surgery,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of biochemistry and molecular biology,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of oral function and molecular biology,ohu university,school of dentistry,fukushima 963-8611, Japan, department of biochemistry and molecular biology,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan, department of oral surgery,kanagawa dental college,kanagawa 238-8580,japan,oral health science research center,kanagawa dental college,kanagawa 238-8580, Japan
 
     
   
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