RRC ID |
12772
|
著者 |
Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, Ishikawa Y, Nomura K, Yokoo H, Shimizu T, Ogata E, Miyazono K, Shimizu K, Imamura T.
|
タイトル |
Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line.
|
ジャーナル |
Cancer Sci
|
Abstract |
Transforming growth factor (TGF)-beta signaling has been shown to promote tumor growth and metastasis in advanced cancer. Use of inhibitors of TGF-beta signaling may thus be a novel strategy for treatment of patients with such cancers. In this study, we investigated the effects of a novel TGF-beta type I receptor (TbetaR-I) kinase inhibitor, Ki26894, on bone metastasis of a highly bone-metastatic variant of human breast cancer MDA-MB-231 cells, termed MDA-MB-231-5a-D (MDA-231-D). Ki26894 blocked TGF-beta signaling in MDA-231-D cells, as detected by suppression of phosphorylation of Smad2 and inhibition of TGF-beta-responsive reporter activity. Moreover, Ki26894 decreased the motility and the invasion of MDA-231-D cells induced by TGF-beta in vitro. Ki26894 also suppressed transcription of plasminogen activator inhibitor-1 (PAI-1), parathyroid hormone-related protein (PTHrP), and interleukin-11 (IL-11) mRNA of MDA-231-D cells, which were stimulated by TGF-beta. X-ray radiography revealed that systemic Ki26894 treatment initiated 1 day before the inoculation of MDA-231-D cells into the left ventricle of BALB/cnu/nu female mice resulted in decreased bone metastasis of breast cancer cells. Moreover, Ki26894 prolonged the survival of mice inoculated with MDA-231-D cells compared to vehicle-treated mice. These findings suggest that TbetaR-I kinase inhibitors such as Ki26894 may be useful for blocking the progression of advanced cancers.
|
巻・号 |
98(1)
|
ページ |
127-33
|
公開日 |
2007-1-1
|
DOI |
10.1111/j.1349-7006.2006.00357.x
|
PII |
CAS357
|
PMID |
17129361
|
MeSH |
Activin Receptors, Type I / drug effects
Activin Receptors, Type I / pharmacokinetics*
Animals
Antineoplastic Agents / pharmacology*
Bone Neoplasms / drug therapy*
Bone Neoplasms / secondary
Female
Humans
Immunoblotting
In Vitro Techniques
Mammary Neoplasms, Experimental / drug therapy*
Mammary Neoplasms, Experimental / pathology*
Mice
Neoplasm Invasiveness / prevention & control
Neoplasm Metastasis / prevention & control*
Protein Kinase Inhibitors / pharmacology*
Protein Serine-Threonine Kinases
Receptor, Transforming Growth Factor-beta Type I
Receptors, Transforming Growth Factor beta / drug effects
Reverse Transcriptase Polymerase Chain Reaction
|
IF |
4.966
|
引用数 |
138
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
遺伝子材料 |
pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04394) CS-CDF-CG-PRE (RDB04379) |