血管内皮生长因子受体
医学
癌症
血管内皮生长因子A
生物
免疫组织化学
作者
Xiaozhi Lv,Ming‐Yue Zheng,Zi-qing Lin,Meng Zhao,Hong Wang,Wei-sen Zeng
出处
期刊:Oral Diseases
[Wiley]
日期:2016-10-01
卷期号:22 (7): 688-696
被引量:8
摘要
OBJECTIVE To evaluate the antitumor effects of fusion protein hGrB-TV of human granzyme B (hGrB) and truncated vascular endothelial growth factor (tVEGF) on human oral squamous cell carcinoma (OSCC) in vitro and in vivo. METHODS The fusion protein hGrB-TV was expressed and purified from E. coli bacteria by affinity chromatography. The cytotoxcity of hGrB-TV on VEGFR-2 (Flk-1)(+) OSCC cells was analyzed in vitro. The antitumor therapeutic study was conducted on OSCC xenografts in vivo. RESULTS The purified hGrB-TV fusion protein was selectively internalized into VEGFR-2 (Flk-1)(+) OSCC cells and endothelial cells. It can cleave inactive caspase 3 into its active p20 form. The hGrB-TV showed dose-dependent cytotoxicity on VEGFR-2(+) SCC-9 cells. The morphological changes and cytolysis were appeared within dozen minutes. However, no cytotoxicity was observed on VEGFR-2(-) cells. The hGrB alone or tVEGF alone did not have any toxicity on SCC-9 cells. In addition, hGrB-TV treatment completely destroyed the vasculature of the chick chorioallantoic membrane (CAM) in vivo and consequently led to chick embryo development arrest. Most importantly, the fusion protein hGrB-TV inhibited tumor angiogenesis and growth of human OSCC xenografts in nude mice without any apparent toxicity. CONCLUSIONS The fusion protein hGrB-TV specifically inhibits angiogenesis and tumor growth of OSCC; hGrB-TV is a powerful and safe therapeutic molecule for tumor therapy.
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