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|Ref Type||Journal Article|
|Authors||Wu X, Zhang J, Yang S, Kuang Z, Tan G, Yang G, Wei Q, Guo Z|
|Title||Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma.|
|Date||2017 Feb 21|
|Abstract Text||The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy.|
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|Unknown unknown||esophagus squamous cell carcinoma||not applicable||Imetelstat + Radiotherapy||Preclinical - Cell line xenograft||Actionable||In a preclinical study, imetelstat increased sensitivity of human esophageal squamous cell carcinoma cell lines to radiotherapy, resulting in increased apoptosis and decreased survival in culture, and increased apoptosis, decreased proliferation, and reduced tumor growth in mouse models (PMID: 28099140).||28099140|