期刊文献+

肝动脉结扎对转移性人肝癌裸鼠原位移植瘤乏氧的影响 被引量:6

The hypoxic effects of hepatic artery ligation on metastatic human orthotopic hepatoma in nude mice model
原文传递
导出
摘要 目的观察肝动脉结扎(HAL)对转移性人肝癌裸鼠原位移植瘤乏氧的影响。方法采用24只BALB/C—nu/nu裸鼠,建立转移性人肝癌裸鼠原位移植模型;随机分为2组,A组于移植瘤术后2周进行HAL(n=12),B组假手术(Sham)作为对照(n=12)。分别于干预术后2d和4周各随机处死每组中6只荷瘤裸鼠,利用免疫组织化学显色(sP法)和Westernblot检测移植瘤内哌莫硝唑(Pimonidazole)和缺氧诱导因子(HIF)-1α的阳性表达和染色强度,以及血管内皮生长因子(VEGF)蛋白水平和肿瘤组织微血管密度(MVD),并用肺连续切片法计数4周时荷瘤裸鼠肺转移灶。结果与Sham组比较,HAL组移植瘤内Pimonidazole阳性细胞及HIF-1α表达水平在术后2d显著增加(P〈0.05),并且肿瘤组织和血清内VEGF水平[(922.5±59.3)比(349.6±46.5)ng/L,P〈0.01]明显增加。术后4周,荷瘤裸鼠肺转移率较对照组增加(6/6比1/6,P〈0.05),但此时乏氧细胞,VEGF表达和MVD则与对照组比较差异无统计学意义(P〉0.05)。结论HAL促进转移性人肝癌裸鼠原位移植瘤短期乏氧及VEGF表达,但不影响移植瘤长期乏氧效应。 Objective To investigate the hypoxic effects of hepatic artery ligation on metastatic human orthotopic nude mouse model of hepatocellular carcinoma (HCC) and further analyze the changes of angiogenesis in tumor tissues. Methods Human HCC cell line MHCC97L was inoculated into 24 BALB/C nude mice. All these cases were divided equally into HAL and sham-operation subgroups at the lgth day after orthotopic implantation. Six randomly selected nude mice of each subgroup were sacrificed at 2nd and/or 24th day after the second operation respectively, and immunostaining and Western blot were carried out to detect the expression of Pimonidazole and hypoxia inducible factor (HIF) -1α in tumor tissues. The vascular endothelial growth factor (VEGF) level in tumor tissues and serum was determined by Western blot and enzyme-linked immunosorbent assay ( ELISA), respectively. The mean microvessel density (MVD) of intratumoral tissues was analyzed by immunostaining. At the 6th week after orthotopic implantation, the pulmonary metastasis in nude mice bearing HCC was evaluated. Results HAL significantly increased the intensity of Pimonidazole (9.33 ± 2.34 vs 5.00 ± 2.10, P 〈 0.05 ) and the expression level of HIF-1α ( +++ - +++ vs + - ++ ,P 〈0.05) in xenografts at the 2nd day after occlusion of hepatic arterial blood, as compared with sham operation group, but could not augment long-term intratumoral hypoxia. In line with hypoxia, VEGF level in tumor tissues and serum [ (922.5 ± 59.3 ) vs (349.6 ± 46.5 ) ng/L, P 〈 0. 01 ] was significantly higher at the 2nd day after HAL than the controls, and no significant difference was found after 24 days. There was no significant difference in intratumoral MVD between HAL group and sham-operation group ( P 〈 0.05). Conclusion HAL could induce dramatic short-term hypoxia in xenograft HCC and overexpression of VEGF,but had no effects on hypoxia and angiogenesis of tumor for a long time.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2009年第8期988-990,共3页 Chinese Journal of Experimental Surgery
关键词 肝细胞 肝动脉结扎 缺氧 血管内皮生长因子 微血管密度 Carcinoma,hepatocellular Hepatic artery ligation Hypoxia Vascular endothelial growth factor Microvessel density
  • 相关文献

同被引文献86

  • 1Andreas Pircher,Michael Medinger,Joachim Drevs.Liver cancer:Targeted future options[J].World Journal of Hepatology,2011,3(2):38-44. 被引量:7
  • 2郑勇斌,赫杰,谭海燕,陈道达.转基因联合泰素帝治疗耐药结直肠癌[J].中华实验外科杂志,2006,23(7):798-799. 被引量:1
  • 3Zhong-Lin Zhang Zhi-Su Liu Quan Sun.Expression of angiopoietins, Tie2 and vascular endothelial growth factor in angiogenesis and progression of hepatocellular carcinoma[J].World Journal of Gastroenterology,2006,12(26):4241-4245. 被引量:24
  • 4Jain RK,Tong RT,Munn LL.Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension,peritumor edema,and lymphatic metastasis:insights from a mathematical model.Cancer Res,2007,67:2729-2735.
  • 5Ackerman NB, Lien WM, Kondi ES, et al. The blood supply of experimental liver metastases. I. The distribution of hepatic artery and portal vein blood to "small" and "large" tumors. Surgery, 1969,66 : 1067- 1072.
  • 6Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology ,2008,48 : 1312-1327.
  • 7Tian J, Tang ZY, Ye SL, et al. New human hepatocellular carcinoma (I-ICC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer, 1999,81:814-821.
  • 8Liu L, Ren ZG, Shen Y, et al. Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: Relevance of epithelial-mesenchymal transition. Cancer Sci,2010,101 : 120-128.
  • 9Nordsmark M, Loncaster J, Aquino-Parsons C, et al. Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas. Radiother Oncol, 2003,67 : 35- 44.
  • 10Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxiainducible factor I alpha in common human cancers and their metastases. Cancer Res, 1999,59:5830-5835.

引证文献6

二级引证文献17

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部