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Liposome transfected to plasmid-encoding endostatin gene combined with radiotherapy inhibits liver cancer growth in nude mice

Liposome transfected to plasmid-encoding endostatin gene combined with radiotherapy inhibits liver cancer growth in nude mice

作     者:Ai-Qing Zheng Xian-Rang Song Ling Wei Xing-Wu Wang Jin-Ming Yu 

作者机构:Tianjin Medical University Tianjin 300070 China Cancer Research Center Shandong Cancer Hospital Jinan 250117Shandong Province China Department of Radiation Oncology Shandong Cancer Hospital Jinan 250117 Shandong Province China 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2005年第11卷第28期

页      面:4439-4442页

核心收录:

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主  题:Endostatin Human liver cardnoma Radiotherapy Gene therapy 

摘      要:AIM: To evaluate whether intratumoral injection of liposome-endostatin complexes could enhance the antitumor efficacy of radiation theapy in human liver cardnoma (BEL7402) model. METHODS: Recombinant plasmid *** was transfected into human liver carcinoma cell line (BEL7402) with lipofectamine to produce conditioned medium. Then BEL7402 cells and human umbilical vein endothelial cells (HUVECs) were treated with the conditioned medium. Cell cycle and apoptosis were analyzed by flow cytometer and endothelial cell proliferation rates were determined by MTT assay. The antitumor efficacy of endostatin gene combined with ionizing radiation in mouse xenograft liver tumor was observed. RESULTS: Endostatin significantly suppressed the S phase fraction and increased the apoptotic index in HUVECs. In contrast, endostatin treatment had no effect on BEL7402 cell apoptosis (2.1±0.3% vs 8.9±1.3%, t= 8.83, P= 0.009〈0.01) or cell cycle distribution (17.2±2.3% vs 9.8±1.2%, t = 4.94,P = 0.016〈0.05). The MTT assay showed that endostatin significantly inhibited the proliferation of HUVECs by 46.4%. The combination of local endostatin gene therapy with radiation therapy significantly inhibited the growth of human liver carcinoma BEL7402 xenografts, the inhibition rate of tumor size was 69.8% on d 28 compared to the untreated group. The tumor volume in the *** combined with radiation therapy group (249±83 mm^3) was significantly different from that in the untreated group (823±148 mm^3, t= 5.86, P= 0.009〈0.01) or in the pcDNA3 group (717±94 mm^3, t= 6.46, P= 0.003〈0.01). Endostatin or the radiation alone also inhibited the growth of liver tumor in vivo, but their inhibition effects were weaker than those of endostatin combined with radiation, the inhibition rates on d 28 were 44.7% and 40.1%, respectively. CONCLUSION: Endostatin not only significantly suppresses tumor growth but also enhances the antitumor efficacy of radiation therapy in human carcinoma xenograft.

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