Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer.
OBJECTIVE
To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).


METHODS
Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.


RESULTS
Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.


CONCLUSIONS
The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.
Shen
Cong-Xiang
CX
Otolaryngology-Head & Neck Surgery, Zhujiang Hospital, The Southern Medical University, Guangzhou 510282, China.
Wen
Zhong
Z
Qian
Yu-Hong
YH
Mu
Shao-Feng
SF
Guan
Xiao-Fang
XF
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D013937:Thymidine Kinase; C509186:TERT protein, human; D019098:Telomerase