Early growth response protein-1 promoter-mediated synergistic antitumor effect of hTERTC27 gene therapy and 5-Flurorouracil on nasopharyngeal carcinoma.

Abstract

hTERTC27 is a newly constructed polypeptide that can induce telomere dysfunction. To study the synergistic antitumor effects of the hTERTC27 polypeptide driven by the early growth response protein-1 (Egr-1) promoter and chemotherapeutic 5-flurorouracil (5-FU) on nasopharyngeal carcinoma, a series of in vitro and in vivo experiments were performed. The results showed that hTERTC27 expression was significantly increased up to 7.21-folds by the 5-FU-activated Egr-1 promoter in C666-1 cells. Overexpressed hTERTC27 made the cells more sensitive to 5-FU, and additionally, inhibited cell proliferation about 20.41%. Combinational therapy of overexpressed hTERTC27 driven by the 5-FU-activated Egr-1 promoter and 5-FU synergistically inhibited cell proliferation and promoted apoptosis of C666-1 cells for about 4.75-fold and 1.76-fold in comparison with a sole therapy of hTERTC27 or 5-FU in vitro. In vivo experiments showed that overexpressed hTERTC27 driven by 5-FU-activated Egr-1 promoter and 5-FU synergistically reduced tumor volume, tumor weight, and local infiltration, which may be relative to tumor cell apoptosis. These results suggest that combinational therapy of overexpressed hTERTC27, which is driven by the 5-FU-activated Egr-1 promoter, and 5-FU may provide a novel approach to treat nasopharyngeal cancer.

• Authors: Guimiao Lin, Marie Chia-Mi Lin, Suxia Lin, Hong Yao, Shuihong Yu, Wanxian Yi, Gaixia Xu, Samuel Sai-Ming Ng, Siping Chen, Jing Yu, Xiaomei Wang, Baoxue Yang
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 27 Issue 7 Pg. 434-41 (Sep 2012) ISSN: 1557-8852 [Electronic] United States
• PMID: 22947087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Early Growth Response Protein 1
• TERT protein, human
• Telomerase
• Fluorouracil

Topics

• Animals
• Carcinoma
• Cell Growth Processes (drug effects, genetics)
• Cell Line, Tumor
• Combined Modality Therapy
• Early Growth Response Protein 1 (genetics, metabolism)
• Fluorouracil (pharmacology)
• Genetic Therapy (methods)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (drug therapy, genetics, therapy)
• Promoter Regions, Genetic
• Random Allocation
• Telomerase (genetics)
• Transfection
• Xenograft Model Antitumor Assays