文章摘要
王璐,王频,丁宗励,曾楷峰,金海林,朱 宏,施瑞华.HIF-1α沉默对食管鳞癌血管生成拟态相关基因影响的体内研究[J].南京医科大学学报,2011,(3):314~318
HIF-1α沉默对食管鳞癌血管生成拟态相关基因影响的体内研究
Effect of HIF-1α gene silence on the expression of vasculogenic mimicry associated genes in esophageal squamous cancer in vivo
投稿时间:2010-08-23  
DOI:10.7655
中文关键词: 血管生成拟态  缺氧诱导因子-1α  食管鳞癌  移植瘤
英文关键词: vasculogenic mimicry  hypoxia-inducible factor 1α  esophageal squamous cancer  transplanted tumor
基金项目:国家自然科学基金资助(30770991)
作者单位
王璐 南京医科大学第一附属医院消化科,江苏 南京 210029 
王频 南京医科大学第一附属医院消化科,江苏 南京 210029 
丁宗励 南京医科大学第一附属医院消化科,江苏 南京 210029 
曾楷峰 南京医科大学第一附属医院消化科,江苏 南京 210029 
金海林 南京医科大学第一附属医院消化科,江苏 南京 210029 
朱 宏 南京医科大学第一附属医院消化科,江苏 南京 210029 
施瑞华 南京医科大学第一附属医院消化科,江苏 南京 210029 
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中文摘要:
      目的:探讨缺氧诱导因子-1α(HIF-1α)基因沉默对人食管鳞癌细胞体内血管生成拟态相关基因表达的影响?方法:将食管鳞癌Eca109细胞株分为空白对照组(未转染组)?阴性对照组(转染空质粒组)和实验组(稳定转染重组质粒pGCsi-shHIF-1α组),接种裸鼠,观测裸鼠皮下移植瘤生长情况;HE染色观察各组肿瘤的异型性及坏死情况;免疫组化和Western blot法检测HIF-1α与上皮细胞激酶(EPHA2)?血管上皮钙黏附素(VE-cadherin)?基质金属蛋白酶-2(MMP-2)在肿瘤组织中的蛋白表达;RT-PCR检测移植瘤组织中HIF-1α与EPHA2?VE-cadherin?MMP-2的mRNA表达?结果:实验组出瘤时间延迟,生长速度减慢,移植瘤体积及重量明显减少(P < 0.05);HE染色示肿瘤异型性减少,坏死显著增多;免疫组化及Western blot发现实验组 HIF-1α蛋白表达完全沉默,EPHA2?VE-cadherin表达明显减少(P < 0.05);RT-PCR提示实验组中HIF-1α及EPHA2?VE-cadherin?MMP2的mRNA含量均有不同程度减少,其中EPHA2?VE-cadherin减少明显(P < 0.05)?结论:HIF-1α沉默能显著抑制食管鳞癌裸鼠移植瘤的生长,并能有效抑制移植瘤血管生成拟态相关基因EPHA2和VE-cadherin的表达,HIF-1α有可能通过以上2个位点参与食管鳞癌血管生成拟态的调控?
英文摘要:
      Objective: To investigate the effect of hypoxia-induced factor 1α (HIF-1α) gene silence on the expression of vasculogenic mimicry associated genes in human esophageal squamous cancer. Methods:Eca109 cells were divided into normal control group(non-transfection group),negative control group(transfected with empty plasmid) and experimental group(stably transfected with recombinant plasmid pGCsi-shHIF-1α), and were transplanted into nude mice to establish esophageal squamous cancer-bearing nude mice. The growth of transplanted tumor in nude mice were observed. HE staining was conducted to detect atypia and necrosis of tumors in each group. Immunohistochemistry and Western blot were used to observe the protein expression of HIF-1α and epithelial kinase (EPHA2), vascular endothelial cadherin(VE-cadherin), matrix metalloproteinase-2 (MMP-2) in tumor tissue. RT-PCR was adopted to detect the mRNA expression of HIF-1α,EPHA2,VE-cadherin and MMP-2. Results:The tumor formation and growth in experimental group were lower than the control groups. The volume and weight were decreased significantly than the control groups(P < 0.05). HE staining confirmed the significantly decreased atypia and increased necrosis in experimental group. Immunohistochemistry and Western blot results showed that HIF-1α protein expression of the experimental group was silenced, and EPHA2, VE-cadherin expression were decreased significantly (P < 0.05). RT-PCR results suggested that the mRNA levels of HIF-1α and EPHA2, VE-cadherin, MMP2 in experimental group were decreased to a different extent, EPHA2 and VE-cadherin were significantly reduced(P < 0.05). Conclusion:HIF-1α gene silence can suppress the growth of esophageal squamous cancer in vivo and inhibit the VE-cadherin and EPHA2 expression in the formation of vasculogenic mimicry,HIF-1α may participate in the regulation of vasculogenic mimicry through these two sites in esophageal squamous cancer.
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