Combined radiation and suicide gene therapy for Nasopharyngeal Carcinoma: in vitro and in vivo models.
Nasopharyngeal carcinoma (NPC) cells are highly radiosensitive. Historically, the main modality for NPC has been radiotherapy. Now, to explore a novel and more effective approach to NPC therapy, a combined strategy of suicide gene and radiation was developed. The yeast CDglyTK (yCDglyTK) gene controlled by a synthetic CMV-enhanced Egr-1 promoter (CE) was constructed whose expression in NPC CNE-2 cells was detected by Western Blot. The cytotoxicity of the combined radio-gene therapy was assayed by MTT. The conversion rate of 5-FC to 5-FU in vitro and the bio-distribution of 5-FU in vivo were determined by HPLC. An animal study in which yCDglyTK-expressing CNE-2 tumors were treated with 5-FC and radiation was also conducted. The results reveal that yCDglyTK is expressed in CNE-2 cells, the CEyCDglyTK/5-FC system has a potent anti-tumor action in NPC, and the radio-sensitization of Egr-1 promoter plays a key role in the killing of CNE-2 cells and in the conversion of 5-FC to 5-FU. Moreover, the treated tumors regressed significantly, and a significant difference of tumor volumes was observed between the CEyCDglyTK+5-FC+radiation group and the other four groups (P<0.05). The results also showed that suicide gene therapy and radiation have a synergic anti-tumor effect on NPC, and the combined strategy of radio-gene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies.
Tang
Aifa
A
Reproductive Medical Center, Medical Center for Peking University and Hongkong University of Science and Technology in Shenzhen, Shenzhen Hospital, Peking University, Shenzhen, China.
Zhang
Junyi
J
Tang
Yaoyun
Y
Feng
Yong
Y
Wu
Linqiang
L
Pan
Qian
Q
Long
Zhigao
Z
Dai
Heping
H
Zhao
Suping
S
Liu
Ting
T
Chen
Zhuchu
Z
Xia
Kun
K
Xia
Jiahui
J