期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2007
卷号：104
期号：9
页码：3460-3465
DOI：10.1073/pnas.0611660104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Transforming growth factor (TGF)-[beta] plays a pivotal role in regulation of progression of cancer through effects on tumor microenvironment as well as on cancer cells. TGF-[beta] inhibitors have recently been shown to prevent the growth and metastasis of certain cancers. However, there may be adverse effects caused by TGF-[beta] signaling inhibition, including the induction of cancers by the repression of TGF-[beta]-mediated growth inhibition. Here, we present an application of a short-acting, small-molecule TGF-[beta] type I receptor (T[beta]R-I) inhibitor at a low dose in treating several experimental intractable solid tumors, including pancreatic adenocarcinoma and diffuse-type gastric cancer, characterized by hypovascularity and thick fibrosis in tumor microenvironments. Low-dose T[beta]R-I inhibitor altered neither TGF-[beta] signaling in cancer cells nor the amount of fibrotic components. However, it decreased pericyte coverage of the endothelium without reducing endothelial area specifically in tumor neovasculature and promoted accumulation of macromolecules, including anticancer nanocarriers, in the tumors. Compared with the absence of T[beta]R-I inhibitor, anticancer nanocarriers exhibited potent growth-inhibitory effects on these cancers in the presence of T[beta]R-I inhibitor. The use of T[beta]R-I inhibitor combined with nanocarriers may thus be of significant clinical and practical importance in treating intractable solid cancers.
关键词：angiogenesis ; gastric cancer ; molecular targeting therapy ; pancreatic cancer
