title: Overexpression of human telomerase reverse transcriptase C-terminal polypeptide sensitizes HeLa cells to 5-fluorouracil‑induced growth inhibition and apoptosis.
abstract: 5‑Fluorouracil (5‑FU) is a commonly used anti‑tumor chemotherapeutic drug for cervical carcinoma. However, increased drug resistance may occur following several cycles of 5‑FU‑based chemotherapy. Novel strategies of gene therapy for enhancing the sensitivity of cancer cells to 5‑FU chemotherapy have been intensively explored. Human telomerase reverse transcriptase (hTERT)C27 is a newly constructed hTERT C‑terminal polypeptide that is capable of promoting chromosome end‑to‑end fusion during anaphase and inducing telomere dysfunction. In the present study, the effects of hTERTC27 overexpression on 5‑FU‑induced proliferation inhibition and apoptosis were observed. HeLa cells were cultured and transfected with the constructed pcDNA3.1 or pcDNA3.1‑hTERTC27 vectors. Expression of hTERTC27 was detected using western blot analysis and was assessed using MTT assays and flow cytometry. The results demonstrated that overexpressed hTERTC27 increased the sensitivity of the HeLa cells to 5‑FU and significantly inhibited HeLa cell proliferation with 5‑FU treatment. In addition, hTERTC27 overexpression evidently promoted the 5‑FU‑induced apoptosis by increasing the expression of activated caspase‑3 and ‑9 and by downregulating the expression of B‑cell lymphoma 2. The results suggest that hTERTC27 overexpression is a potential clinical strategy for enhancing the antitumor effect of 5‑FU chemotherapy in the treatment of cervical carcinoma.
authors.affiliation: The Engineering Lab of Synthetic Biology and the Key Lab of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Guimiao
authors.initials: G
authors.lastname: Lin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Shuihong
authors.initials: S
authors.lastname: Yu
authors.forename: Suxia
authors.initials: S
authors.lastname: Lin
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.forename: Zhangchi
authors.initials: Z
authors.lastname: Ding
authors.forename: Siping
authors.initials: S
authors.lastname: Chen
authors.forename: Marie Chia-Mi
authors.initials: MC
authors.lastname: Lin
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D053453:Caspase 9; D005472:Fluorouracil