靶向HGF/c-MET可诱导原发性渗出性淋巴瘤的细胞周期停滞、DNA破坏和凋亡
Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo. The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model. By using microarray analysis, we identify many novel genes that are potentially controlled by HGF/c-MET within PEL cells. One of the downstream candidates, ribonucleoside-diphosphate reductase subunit M2 (RRM2), also displays the promising therapeutic value for PEL treatment. Our findings provide the framework for development of HGF/c-MET-focused therapy and implementation of clinical trials for PEL patients. Copyright © 2011 by The American Society of Hematology; all rights reserved.
上一篇: 椎间盘中的Collagen-Derived N-Acetylated Proline-Glycine-Proline可调节软骨终板干细胞中的CXCR1/2表达和活化以诱导向促炎表型移行和分化
来源: Scopus
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