http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Lyu, Junfang,Yang, Eun Ju,Head, Sarah A.,Ai, Nana,Zhang, Baoyuan,Wu, Changjie,Li, Ruo-Jing,Liu, Yifan,Yang, Chen,Dang, Yongjun,Kwon, Ho Jeong,Ge, Wei,Liu, Jun O.,Shim, Joong Sup Elsevier 2017 Cancer letters Vol.409 No.-
<P><B>Abstract</B></P> <P>Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A phenotypic screen identified 13 existing drugs, including cepharanthine, as cholesterol trafficking inhibitors. </LI> <LI> Cepharanthine inhibited lysosomal cholesterol trafficking by binding to NPC1 protein and increasing the lysosomal pH. </LI> <LI> The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes. </LI> <LI> Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. </LI> <LI> Cepharanthine treatment enhanced the antitumor activity of cisplatin in lung and breast cancer xenografts in mice. </LI> </UL> </P>
Haitao Zheng,Meng Wang,Lixin Jiang,Haidi Chu,Jinchen Hu,Jinyao Ning,Baoyuan Li,Dong Wang,Jie Xu 대한암학회 2016 Cancer Research and Treatment Vol.48 No.2
Purpose The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. Materials and Methods Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. Results Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. Conclusion These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.