Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer.

Abstract

BACKGROUND/AIM:

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).

MATERIALS/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.

CONCLUSION:

The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.

• Authors: Cong-Xiang Shen, Zhong Wen, Yu-Hong Qian, Shao-Feng Mu, Xiao-Fang Guan
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 29 Pg. 94 (Jul 13 2010) ISSN: 1756-9966 [Electronic] England
• PMID: 20626878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Thymidine Kinase
• TERT protein, human
• Telomerase

Topics

• Animals
• Blotting, Western
• Breast Neoplasms (enzymology, genetics, therapy)
• Cell Proliferation
• Cells, Cultured
• Cytomegalovirus (genetics)
• Endothelium, Vascular (cytology, metabolism)
• Enhancer Elements, Genetic (genetics)
• Genetic Therapy
• Genetic Vectors
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nasopharyngeal Neoplasms (enzymology, genetics, therapy)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics)
• Regulatory Sequences, Nucleic Acid
• Reverse Transcriptase Polymerase Chain Reaction
• Telomerase (genetics)
• Thymidine Kinase (genetics, metabolism)