TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting microenvironmental platelet-derived growth factor signaling.
Anticancer Res
; 35(3): 1423-31, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25750293
ABSTRACT
BACKGROUND:
TSU-68 is a multikinase inhibitor that targets platelet-derived growth factor receptors (PDGFRs). In the present study, we evaluated the effect of TSU-68 on the tumor-microenvironment interaction in hepatocellular carcinoma (HCC). MATERIALS ANDMETHODS:
HCC and fibroblast cell lines (HuH7, Hep3B, HuH1 and WI-38) were used to evaluate their interactions. Cancer characteristics were evaluated by spheroid formation and tumorigenicity in immunodeficient mice. Time-lapse image analysis was performed to monitor cell motility.RESULTS:
Although PDGFA was abundantly expressed, PDGFR-α was predominantly located in the cytoplasm and was not functional in HuH7 cells. Co-culture experiments demonstrated that HCC cells induced phosphorylation of PDGFR-α in WI-38 fibroblasts and that stimulated fibroblasts, in turn, boosted the spheroid formation capacity of HCC cells. TSU-68 inhibited phosphorylation of PDGFR-α in WI-38 cells and suppressed the growth of subcutaneously co-injected HuH7/WI-38 tumor xenografts.CONCLUSION:
TSU-68 inhibits stromal PDGF signaling activated by cancer cells and suppresses HCC growth.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propionatos
/
Fator de Crescimento Derivado de Plaquetas
/
Transdução de Sinais
/
Carcinoma Hepatocelular
/
Indóis
/
Neoplasias Hepáticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Japão