The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs.
Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast CD, yeast CD/UPRT, and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by RT-PCR and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-FC and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p < 0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies.
National Laboratory of Medical Genetics of China, Central South University, Changsha, China.
Jiahui
J
Xia
Kun
K
Xia
Yong
Y
Feng
Aifa
A
Tang
Yaoyun
Y
Tang
Lingqian
L
Wu
Desheng
D
Liang
Fang
F
Cai
Qian
Q
Pan
Zhigao
Z
Long
Heping
H
Dai
Yunyi
Y
Zhang
Suping
S
Zhao
Zhuchu
Z
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011829:Radiation Dosage; D011878:Radiotherapy / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005437:Flucytosine