Effect of adenovirus-E1A gene therapy on in vivo radiosensitivity to nasopharyngeal cancer.
- Author:
Rongrong ZHOU
1
;
Jia CHEN
;
Zhiqiang XIAO
Author Information
1. Department of Oncology, Xiangya Hospital, Central South University,Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Adenovirus E1A Proteins;
biosynthesis;
genetics;
Animals;
Apoptosis;
physiology;
Cell Line, Tumor;
Genetic Therapy;
methods;
Humans;
Mice;
Mice, Nude;
Nasopharyngeal Neoplasms;
blood supply;
pathology;
radiotherapy;
Neoplasm Transplantation;
Radiation Tolerance;
genetics;
Random Allocation;
Vascular Endothelial Growth Factor A;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2009;34(8):744-751
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To determine the effect of Ad-E1A gene therapy on in vivo radiosensitivity to nasopharyngeal carcinoma.
METHODS:CNE-2Z cells (2 x 10(5)) were subcutaneously injected into nude mice to develop tumor (1-3 mm) 6 days later. The tumor-bearing mice were then randomly divided into 6 groups (10 mice per group) for PBS treatment or treatment with radiotherapy, Ad-E1A, or Ad-beta-gal alone or radiotherapy in combination with Ad-E1A or Ad-beta-gal. The mice were treated with Ad-E1A or Ad-beta-gal (5 x 10(9) plaque forming units) by intratumoral injection twice weekly for 2 weeks at beginning of week 2. The mice treated with radiotherapy in combination with Ad-E1A or Ad-beta-gal received 2 Gy radiotherapy daily for 5 days following the first week of treatment with Ad-E1A or Ad-beta-gal. Control mice received PBS therapy or radiotherapy only after tumor cells were injected. When the size of tumor exceeded 2 cm, the mice were killed and the tumors underwent immunohistochemical analysis for VEGF and CD34 expression and TUNEL assay for apoptosis.
RESULTS:The growth delay time was longest in the Ad-E1A plus radiotherapy group. Tumors treated with Ad-E1A plus radiotherapy were 4.7-fold smaller than those treated with radiotherapy alone and 5.3-fold smaller than those treated with Ad-E1A alone. The survival rate of tumor-bearing mice treated with Ad-E1A plus radiotherapy was significantly higher than that of other treatment groups. The vessel density and the VEGF expression were significantly lower in tumors treated with Ad-E1A plus radiotherapy than those treated with radiotherapy alone, Ad-E1A alone, Ad-beta-gal alone, or Ad-beta-gal plus radiotherapy (P<0.01). TUNEL staining revealing apoptosis can be detected in the Ad-E1A group, radiotherapy group, Ad-E1A plus radiotherapy group, and more apoptosis can be detected in tumors treated with Ad-E1A plus radiotherapy than those of other treatment groups.
CONCLUSION:E1A gene therapy can effectively enhance the nasopharyngeal carcinoma sensitivity to the radiotherapy by down-regulating VEGF expression and inducing apoptosis.
