摘要
目的探索人端粒酶逆转录酶启动子（hTERTp）介导自杀基因辣根过氧化酶（HRP）-吲哚乙酸（IAA）系统联合射线，对相同来源而放射敏感性不同的人喉癌移植瘤模型的治疗作用。方法建奇相同来源而放射敏感性不同的人喉癌（Hep-2和Hep-2R细胞）移植瘤模型，并分为联合治疗组（A组和AR组）、基因治疗组（B组和BR组）、单纯放射组（C组和CR组）和对照组（D组和DR组）。瘤内注射脂质体包裹的质粒phTERTp—HRP，腹腔内注射IAA并联合放疗30Gy，观察对移植瘤生长的抑制作用。应用原位末端转移酶标记技术（TUNEL）检测肿瘤细胞的凋亡情况；应用AP法检测瘤内HRP蛋白的表达。结果裸鼠移植瘤生长以联合治疗组最慢，以对照组最快。A组的肿瘤抑制率为54．8％，B组为10．0％，C组为31．9％，AR组为52．7％，BR组为24．8％，CR组为17．0％。A组和AR组可见大量肿瘤细胞坏死和凋亡，凋亡指数分别为16．6％±1．3％和17．6％±1．3％，高于其他组（P〈0．05）。B组的HRP蛋白表达率（21．9％±5．7％）低于BR组和（33．3％±8．9％），辐射诱导后，A组和AR组的HRP蛋白表达率分别增加2．1和1．6倍（P〈0．05）。结论在不同放射敏感性的喉癌移植瘤模型中，hTERTp能被射线诱导，并根据瘤内端粒酶活性增强HRP基因的表达。hTERTp—HRP—IAA系统通过诱导肿瘤细胞凋亡和引起细胞坏死，抑制裸鼠移植瘤生长，并与射线协同作用，起到放射增敏作用。
Objective To explore the therapeutic efficiency of human telomerase reverse transcriptase promoter （hTERTp） mediated horseradish peroxidase （HRP） catalyzed effects of indole-3-acetic （IAA） on laryngeal squamous cell carcinoma with different radiosensitivity in vivo. Methods Human laryngeal squamous cell carcinoma Hep-2 and Hep-2R cells were transplanted into nude mice. After growing to about 30 - 50 mm^3 , the tumor-bearing mice were randomly divided into eight groups ： Hep-2 line ： combined group （ A）, gene group （ B）, radiation group （C） and blank group （D） ; Hep-2R line： combined group （ AR ）, gene group （BR ）, radiation group （CR ） and blank group （DR ）. The phTERTp-HRP was delivered by intratumoral injection and the IAA by intraperitoneal injection, combined with 2 Gy daily radiation to a total dose of 30 Gy. The tumor volume was recorded. The cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay. The expression of HRP protein was detected by AP immunohistochemisty. Results The tumor growth of combined groups was attenuated significantly and the tumor volume of Hep-2R blank group was the largest. The inhibition rate of each group was： A： 54.8%, B： 10.0%, C： 31.9%; AR： 52.7%, BR： 24.8%, CR： 17.0%. In the combined groups, necrosis and apoptosis of tumor cells were observed under the light microscope and the apoptotic index [ A （16.6 ± 1. 3）% vs. AR（17.6 ± 1. 3）%]of tumor cells was highest （P 〈0.05）. The HRP protein expression or BR（33.3 ±8.9）% was higher than that of B （21.9±5.7）%, which was directly up-regulated in the tumors （45.0% vs. 54.8% , P 〈 0.05 ） after radiation. Conclusion In the Hep-2- and Hep-2R-transplantation tumors in nude mice, hTERTp can be induced by radiation and enhance the expression of horseradish peroxidase （HRP） gene according to telomerase activity, hTERTp-HRP/IAA system, which has synergistic effects with radiation and in
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2008年第10期733-736,共4页
Chinese Journal of Oncology
基金
国家自然科学基金资助项目（30672438）
湖北省自然科学基金创新群体资助项目（2006ABC009）
关键词
人端粒酶逆转录酶启动子
基因放疗
喉肿瘤
裸鼠
Human telomerase reverse transcriptase promoter
Gene-radiation therapy
Laryngeal neoplasms
Nude mice
