Zheng Ai-Qing, Song Xian-Rang, Yu Jin-Ming, Wei Ling, Wang Xing-Wu
Cancer Research Center, Shandong Cancer Hospital, Jinan 250117, Shandong Province, China.
World J Gastroenterol. 2005 Jul 28;11(28):4439-42. doi: 10.3748/wjg.v11.i28.4439.
To evaluate whether intratumoral injection of liposome-endostatin complexes could enhance the antitumor efficacy of radiation therapy in human liver carcinoma (BEL7402) model.
Recombinant plasmid pcDNA3.End 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.
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 pcDNA3.End combined with radiation therapy group (249+/-83 mm3) was significantly different from that in the untreated group (823+/-148 mm3, t = 5.86, P = 0.009<0.01) or in the pcDNA3 group (717+/-94 mm3, 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.
Endostatin not only significantly suppresses tumor growth but also enhances the antitumor efficacy of radiation therapy in human carcinoma xenograft.
评估瘤内注射脂质体-内皮抑素复合物是否能增强人肝癌（BEL7402）模型中放射治疗的抗肿瘤疗效。
用脂质体将重组质粒pcDNA3.End转染到人肝癌细胞系（BEL7402）中以产生条件培养基。然后用该条件培养基处理BEL7402细胞和人脐静脉内皮细胞（HUVECs）。通过流式细胞仪分析细胞周期和凋亡情况，并用MTT法测定内皮细胞增殖率。观察内皮抑素基因联合电离辐射对小鼠异种移植肝癌的抗肿瘤疗效。
内皮抑素显著抑制HUVECs的S期比例并增加凋亡指数。相比之下，内皮抑素处理对BEL7402细胞凋亡（2.1±0.3%对8.9±1.3%，t = 8.83，P = 0.009<0.01）或细胞周期分布（17.2±2.3%对9.8±1.2%，t = 4.94，P = 0.016<0.05）无影响。MTT法显示内皮抑素显著抑制HUVECs的增殖达46.4%。局部内皮抑素基因治疗与放射治疗联合显著抑制人肝癌BEL7402异种移植瘤的生长，与未治疗组相比，第28天时肿瘤大小的抑制率为69.8%。pcDNA3.End联合放射治疗组的肿瘤体积（249±83 mm³）与未治疗组（823±148 mm³，t = 5.86，P = 0.009<0.01）或pcDNA3组（717±94 mm³，t = 6.46，P = 0.003<0.01）有显著差异。单独使用内皮抑素或放射治疗也能在体内抑制肝癌生长，但它们的抑制作用弱于内皮抑素联合放射治疗，第28天时的抑制率分别为44.7%和40.1%。
内皮抑素不仅能显著抑制肿瘤生长，还能增强人癌异种移植模型中放射治疗的抗肿瘤疗效。
