位置:成果数据库 > 期刊 > 期刊详情页
人端粒酶逆转录酶启动子在裸鼠中增强人喉癌对基因放射治疗的敏感性
  • 期刊名称:中华肿瘤杂志 2009 30(10): 733-736.
  • 时间:0
  • 分类:R730.54[医药卫生—肿瘤;医药卫生—临床医学] R730.55[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]武汉大学中南医院放化疗科肿瘤生物学行为湖北省重点实验室,430071
  • 相关基金: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)
  • 相关项目:(CArG)n-hTERT嵌合启动子及其调控的HRP/IAA前药系统的靶向抗肿瘤作用
中文摘要:

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。

英文摘要:

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

同期刊论文项目
同项目期刊论文