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国家高技术研究发展计划(2002AA216111)

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发文基金:国家高技术研究发展计划国家自然科学基金更多>>
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Expression of vascular endothelial growth factor and its receptors KDR and Fit-1 in gastric cancer cells被引量:77
2002年
AIM: The expression of vascular endothelial growth factor (VEGF) and its receptors KDR and Flt-1 by gastric carcinoma tissues and different gastric carcinoma cell lines was detected to elucidate the molecular mechanism of this growth factor in promoting tumor growth.METHODS: The expression of VEGF, Flt-1 and KDR was determined by reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer cell lines RF-1, RF-48,AGS-1, NCI-N87, NCI-SNU-1, NCI-SNU-5, NCI-SNU-16 and KATO-Ⅲ. The expression of Flt-1 and KDR in paraffinembedded specimens of gastric cancer was determined by immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the role of VEGF in tumor cell proliferation.RESULTS: All 8 gastric cancer cell lines analyzed expressed VEGF121 and VEGF16s and six of them expressed both Flt-1 and KDR, while cell line NCI-SNU-5 expressed Flt-1 only and cell line KATOⅢ expressed neither Flt-1 nor KDR. The gastric carcinoma tissues expressed Flt-1 and KDR widely,with the positive rate of expression of Flt-1 and KDR being 84.6 % and 70 % respectively. The exogenous VEGF stimulated the growth of KDR-positive cell lines NCI-N87 and AGS-1 in a dose-dependent manner but exhibited no effect on the growth of KDR-negative cell line NCI-N87.CONCLUSION: VEGF and its receptors KDR and Flt-1 were expressed widely in gastric carcinoma cells and the VEGF stimulated KDR-positive tumor cell growth directly. These results suggest that VEGF may play a role in promoting tumor growth and metastasis by participating in both paracrine and autocrine pathways.
Hua Zhang Jian Wu Lin Meng Cheng-Chao Shou,Peking University School ofOncology,Beij ing Institute for Cancer Research,Beijing 100034,China
关键词:VEGF受体KDRFLT-1胃癌细胞
外源p53基因和抗血管生成小肽F56联合对小鼠乳腺癌移植瘤生长和转移的抑制作用被引量:4
2007年
目的:观察腺病毒介导的野生型p53基因联合抗血管生成小肽F56对乳腺癌移植瘤及其肺转移灶的抑制作用。方法:将人乳腺癌BICR-H1细胞接种于裸鼠或NOD/SCID小鼠乳垫内。成瘤后,裸鼠随机分成Adp53+F56组、Adp53组、F56组和空白对照组,NOD/SCID小鼠则随机分成Adp53+F56组、Adp53组、F56组、Adlacz组和空白对照组,分别采用腺病毒p53、F56或二者联合治疗,以小肽溶剂作对照,NOD/SCID小鼠还加用腺病毒空载体(Adlacz)作对照。观察裸鼠移植肿瘤体积、组织病理学改变,用免疫组织化学方法检测肿瘤p53、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达及微血管密度(microrascular density,MVD);观察NOD/SCID小鼠移植瘤的肺转移情况。结果:p53基因、F56及二者联合治疗均能明显抑制裸鼠移植瘤生长,但以联合治疗组最显著,Adp53+F56组、Adp53组、F56组和空白对照组肿瘤最终的相对生长体积分别为2.47、4.37、4.69和12.49;免疫组织化学检测发现,Adp53+F56组和Adp53组肿瘤内p53表达增高,P53阳性率分别增高了9.4%、6.3%,但与空白对照组比较,差异无统计学意义(P=0.693);Adp53+F56组、Adp53组、F56组VEGF表达下降,VEGF阳性率分别下降21.9%、9.4%和3.1%,但与空白对照组比较,差异亦无统计学意义(P=0.284);Adp53+F56组、Adp53组、F56组MVD分别为14.50±2.54、16.28±3.44和18.06±7.66,与空白对照组(24.93±6.53)比较,差异有统计学意义(P=0.000),且Adp53+F56组、Adp53组、F56组瘤内出现坏死,并以Adp53+F56组最为明显。NOD/SCID小鼠Adp53+F56组、Adp53组、F56组肺转移灶平均数目分别为1.143±0.378,2.750±0.886,3.375±0.518,较Adlacz组(5.000±0.816)和空白对照组(5.670±0.817)都显著减少(P=0.000),尤以Adp53+F56组最少。结论:p53基因联合抗肿瘤血管生成小肽F56可显著抑制肿瘤的生长和转移。p53基因影响肿瘤生长与转移的因素之一可能与p53对VEGF的抑制作用有一定关系。
肖绍文颜博杨敬贤寿成超张珊文
关键词:血管内皮生长因子类腺病毒科
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