基础医学与临床 ›› 2014, Vol. 34 ›› Issue (5): 648-653.

• 研究论文 • 上一篇    下一篇

高强度聚焦超声治疗对肝癌细胞裸鼠移植瘤低氧诱导因子表达和细胞凋亡的影响

付志豪1,武伦1,乔正荣2,周世骥3,李生伟1   

  1. 1. 重庆医科大学附属第二医院
    2. 重庆医科大学附属第一医院血管外科
    3. 重庆医科大学第二临床学院肝胆外科
  • 收稿日期:2013-06-21 修回日期:2014-03-21 出版日期:2014-05-05 发布日期:2014-04-28
  • 通讯作者: 李生伟 E-mail:lswgg@126.com
  • 基金资助:
    国家自然科学基金面上资助项目;重庆市卫生局重点资助项目;重庆市卫生局重点资助项目

Effect of HIFU on hypoxia-inducible factor (HIF-1α) expression and cell apoptosis in liver cancer cell xenografts of nude mice

  • Received:2013-06-21 Revised:2014-03-21 Online:2014-05-05 Published:2014-04-28

摘要: 目的 探讨高强度聚焦超声(HIFU)治疗后的残余肝癌组织中低氧诱导因子(HIF-1α)、P53和凋亡的变化及关系。方法 建立肝癌HpG2细胞株裸鼠移植瘤模型30只,采用CZF-Ⅱ型HIFU治疗仪治疗,随机分为对照组、治疗后1、3及5d和1及2周组。HE染色观察标本病理变化;TUNEL法检测残余癌组织凋亡及计算凋亡指数;免疫组化、Western blot和实时荧光定量 PCR技术检测HIF-1α、P53蛋白和mRNA水平。结果 治疗后有残余肿瘤细胞和大片坏死区域。与其他组相比,凋亡指数在3d组显著升高(P<0.05),在5d、1和2周组逐渐下降。HIF-1α和P53蛋白在各组中出现强弱不同的表达。HIF-1α和P53蛋白和mRNA在治疗后1~3天表达逐渐升高,在3d组显著高于其他组(P<0.05),在5d、1和2周组逐渐下降。结论 HIFU治疗肝癌细胞裸鼠移植瘤后可以促进残余癌细胞凋亡,此可能与HIF-1α、P53基因表达异常关系密切。

关键词: 肝癌、缺氧诱导因子、凋亡

Abstract: Objective To study the effects of hypoxia-inducible factor (HIF-1α) and apoptosis of the residual tumor cells in nude mice after treatment by high- intensity focused ultrasound (HIFU).Methods Human HCC implantation was established in 30 nude mice. CZF-Ⅱ HIFU therapeutic apparatus were used for treatment .Nude mice were randomly divided into control group and treatment group (included 1d group, 3d group, 5d group, 1w group,and 2w group). Pathological changes were observed with HE staining;Cell apoptosis were detected by DNA agarose gel electrophoresis and terminal deoxynucleotidyltransferase-mediated Dutp nick end-labeling (TUNEL) assay; SP immunohistochemistry was used to detect HIF-1α protein;Western blot and Real-time quantitative PCR were used to detect HIF-1α, P53 protein and mRNA expression levels. Results HE showed that there were residual tumor cells and large necrotic areas after treatment. Compared with other groups, the apoptosis index in 3d group was significantly higher (P <0.05),in the 5d group,1w group,2w group gradually decreased. Immunohistochemistry showed that the expression of HIF-1α, P53 protein was different in each group. Compared with other groups,Western blot and RT-PCR showed an increase of HIF-1α, P53 protein and mRNA levels in groups after treatment of 1 to 3 days, and peaked in 3d group(P <0.05). Conclusion HIFU treatment can induce consistent apoptosis in residual tumor, which may be related with disordered expression of HIF-1α and P53.

Key words: liver neoplasms、hypoxia-inducible factor、apoptosis

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