[Effect of adenovirus-E1A gene therapy on in vivo radiosensitivity to nasopharyngeal cancer].
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.


CONCLUSIONS
E1A gene therapy can effectively enhance the nasopharyngeal carcinoma sensitivity to the radiotherapy by down-regulating VEGF expression and inducing apoptosis.
Zhou
Rongrong
R
Department of Oncology, Xiangya Hospital, Central South University,Changsha 410008, China.
Chen
Jia
J
Xiao
Zhiqiang
Z
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*; D009368:Neoplasm Transplantation; D011836:Radiation Tolerance / Q000235:genetics*; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse