hTERT promoter enhances the radiosensitivity to gene-radiation therapy of human laryngeal carcinoma transplanted in nude mice.
- Author:
Cheng-hu HUANG
1
;
Zheng-kai LIAO
;
Fu-xiang ZHOU
;
Wei-feng WANG
;
Cong-hua XIE
;
Hong-yan ZHANG
;
Wen-jie SUN
;
Yun-feng ZHOU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; Cell Line, Tumor; Combined Modality Therapy; Female; Genetic Therapy; methods; Horseradish Peroxidase; genetics; metabolism; Humans; Indoleacetic Acids; metabolism; pharmacology; Laryngeal Neoplasms; metabolism; pathology; therapy; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Promoter Regions, Genetic; Radiation Tolerance; Radiotherapy; methods; Random Allocation; Telomerase; genetics; Tumor Burden
- From: Chinese Journal of Oncology 2008;30(10):733-736
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSHuman laryngeal squamous cell carcinoma Hep-2 and Hep-2R cells were transplanted into nude mice. After growing to about 30 approximately 50 mm3, 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.
RESULTSThe 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 of 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.
CONCLUSIONIn 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 inhibits the tumor growth by induction of apoptosis and necrosis, may be a new gene-radiation strategy for the treatment of laryngeal carcinoma.
