title: 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.affiliation: Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun, China.
authors.forename: Guimiao
authors.initials: G
authors.lastname: Lin
authors.forename: Marie Chia-Mi
authors.initials: MC
authors.lastname: Lin
authors.forename: Suxia
authors.initials: S
authors.lastname: Lin
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.forename: Shuihong
authors.initials: S
authors.lastname: Yu
authors.forename: Wanxian
authors.initials: W
authors.lastname: Yi
authors.forename: Gaixia
authors.initials: G
authors.lastname: Xu
authors.forename: Samuel Sai-Ming
authors.initials: SS
authors.lastname: Ng
authors.forename: Siping
authors.initials: S
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D002277:Carcinoma; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D011401:Promoter Regions, Genetic; D011897:Random Allocation; D019098:Telomerase / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D051766:Early Growth Response Protein 1; C509186:TERT protein, human; D019098:Telomerase; D005472:Fluorouracil